Intra-tumour heterogeneity : going beyond genetics

© 2016 Federation of European Biochemical Societies Cancer patients die primarily due to disease recurrence after transient treatment responses. The emergence of therapy-resistant escape variants is fuelled by intra-tumour heterogeneity, underpinned by interference and Darwinian evolution among cont...

Full description

Saved in:
Bibliographic Details
Published inThe FEBS journal Vol. 283; no. 12; pp. 2245 - 2258
Main Authors Caiado, Francisco, Silva-Santos, Bruno, Norell, Haakan
Format Journal Article
LanguageEnglish
Published England John Wiley & Sons, Inc 01.06.2016
Blackwell Publishing Ltd
Subjects
Cancer
Cancer mutation
Cancer stem cells
Cell Lineage - genetics
Clonal evolution
Epigenesis, Genetic
Evolution & development
Evolution, Molecular
Gene expression
Gene Expression Regulation, Neoplastic
Genetic Fitness
Genetic Heterogeneity
Genetics
Humans
Leukaemia initiating cells
Lineage tracing
Mutation
Neoplasms - genetics
Neoplasms - pathology
next‐generation sequencing
non‐genetic variability
Population dynamics
single‐cell transcriptomics
sub‐clone
Tumor Microenvironment - genetics
cancer mutation
single-cell transcriptomics
clonal evolution
leukaemia initiating cells
next-generation sequencing
non-genetic variability
sub-clone
cancer stem cells
lineage tracing
population dynamics
Online AccessGet full text

Cover

Abstract © 2016 Federation of European Biochemical Societies Cancer patients die primarily due to disease recurrence after transient treatment responses. The emergence of therapy-resistant escape variants is fuelled by intra-tumour heterogeneity, underpinned by interference and Darwinian evolution among continuously developing sub-clones in the mutating tumour. Novel cancer cell variants build upon the pre-existing genetic landscape and tumour heterogeneity is often ascribed largely to genetic variability. While mutations are required for cancer development and studies of genetic evolution of tumours have improved our understanding of cancer biology, genetics only represents one dimension of the fitness of each cancer cell. Beyond the mutations, several non-genetic factors also add significant variability, resulting in a complex and highly dynamic tumour cell population that can drive disease under almost any condition. This viewpoint article summarizes the genetic basis of intra-tumour heterogeneity, before dissecting four major interdependent non-genetic factors we think critically contribute to the overall variability of tumour cells in all types of cancer: epigenetic regulation, cellular differentiation hierarchies, gene expression stochasticity and tumour microenvironment. We finally present the relevant technological approaches to address the combined contribution of both genetic and non-genetic factors to intra-tumour heterogeneity, focusing on genomic profiling, cellular lineage tracing and single-cell RNA sequencing technologies. This strategy will ultimately allow dissection of the full range and depth of intra-tumour heterogeneity. We thus believe that understanding how cancer genetics synergize with the emerging non-genetic factors will be key for development of therapies able to tackle tumour escape and thereby improve cancer patient survival. Our work was funded by Associação Portuguesa Contra a Leucemia (APCL-SEMAPA 2014 to HN) and Fundação para a Ciência e Tecnologia (FCT) through individual fellowships (SFRH/BPD/91344/2012 to FC; SFRH/BCC/105888/2014 and SFRH/BPD/112968/2015 to HN) and a FCT research grant (EXPL/BIM-ONC/1656/2013 to HN).
AbstractList Cancer patients die primarily due to disease recurrence after transient treatment responses. The emergence of therapy-resistant escape variants is fuelled by intra-tumour heterogeneity, underpinned by interference and Darwinian evolution among continuously developing sub-clones in the mutating tumour. Novel cancer cell variants build upon the pre-existing genetic landscape and tumour heterogeneity is often ascribed largely to genetic variability. While mutations are required for cancer development and studies of genetic evolution of tumours have improved our understanding of cancer biology, genetics only represents one dimension of the fitness of each cancer cell. Beyond the mutations, several non-genetic factors also add significant variability, resulting in a complex and highly dynamic tumour cell population that can drive disease under almost any condition. This viewpoint article summarizes the genetic basis of intra-tumour heterogeneity, before dissecting four major interdependent non-genetic factors we think critically contribute to the overall variability of tumour cells in all types of cancer: epigenetic regulation, cellular differentiation hierarchies, gene expression stochasticity and tumour microenvironment. We finally present the relevant technological approaches to address the combined contribution of both genetic and non-genetic factors to intra-tumour heterogeneity, focusing on genomic profiling, cellular lineage tracing and single-cell RNA sequencing technologies. This strategy will ultimately allow dissection of the full range and depth of intra-tumour heterogeneity. We thus believe that understanding how cancer genetics synergize with the emerging non-genetic factors will be key for development of therapies able to tackle tumour escape and thereby improve cancer patient survival. Intra-tumour heterogeneity contributes to cancer therapy failure and is ascribed largely to genetic variability between sub-clones. We discuss the impact of key non-genetic factors that also underpin intra-tumour heterogeneity and the technological approaches employed to dissect them. The combined study of both genetic and non-genetic factors that collectively diversify cancer cell populations represents an important frontier to achieve curative treatments.
Cancer patients die primarily due to disease recurrence after transient treatment responses. The emergence of therapy‐resistant escape variants is fuelled by intra‐tumour heterogeneity, underpinned by interference and Darwinian evolution among continuously developing sub‐clones in the mutating tumour. Novel cancer cell variants build upon the pre‐existing genetic landscape and tumour heterogeneity is often ascribed largely to genetic variability. While mutations are required for cancer development and studies of genetic evolution of tumours have improved our understanding of cancer biology, genetics only represents one dimension of the fitness of each cancer cell. Beyond the mutations, several non‐genetic factors also add significant variability, resulting in a complex and highly dynamic tumour cell population that can drive disease under almost any condition. This viewpoint article summarizes the genetic basis of intra‐tumour heterogeneity, before dissecting four major interdependent non‐genetic factors we think critically contribute to the overall variability of tumour cells in all types of cancer: epigenetic regulation, cellular differentiation hierarchies, gene expression stochasticity and tumour microenvironment. We finally present the relevant technological approaches to address the combined contribution of both genetic and non‐genetic factors to intra‐tumour heterogeneity, focusing on genomic profiling, cellular lineage tracing and single‐cell RNA sequencing technologies. This strategy will ultimately allow dissection of the full range and depth of intra‐tumour heterogeneity. We thus believe that understanding how cancer genetics synergize with the emerging non‐genetic factors will be key for development of therapies able to tackle tumour escape and thereby improve cancer patient survival.
© 2016 Federation of European Biochemical Societies Cancer patients die primarily due to disease recurrence after transient treatment responses. The emergence of therapy-resistant escape variants is fuelled by intra-tumour heterogeneity, underpinned by interference and Darwinian evolution among continuously developing sub-clones in the mutating tumour. Novel cancer cell variants build upon the pre-existing genetic landscape and tumour heterogeneity is often ascribed largely to genetic variability. While mutations are required for cancer development and studies of genetic evolution of tumours have improved our understanding of cancer biology, genetics only represents one dimension of the fitness of each cancer cell. Beyond the mutations, several non-genetic factors also add significant variability, resulting in a complex and highly dynamic tumour cell population that can drive disease under almost any condition. This viewpoint article summarizes the genetic basis of intra-tumour heterogeneity, before dissecting four major interdependent non-genetic factors we think critically contribute to the overall variability of tumour cells in all types of cancer: epigenetic regulation, cellular differentiation hierarchies, gene expression stochasticity and tumour microenvironment. We finally present the relevant technological approaches to address the combined contribution of both genetic and non-genetic factors to intra-tumour heterogeneity, focusing on genomic profiling, cellular lineage tracing and single-cell RNA sequencing technologies. This strategy will ultimately allow dissection of the full range and depth of intra-tumour heterogeneity. We thus believe that understanding how cancer genetics synergize with the emerging non-genetic factors will be key for development of therapies able to tackle tumour escape and thereby improve cancer patient survival. Our work was funded by Associação Portuguesa Contra a Leucemia (APCL-SEMAPA 2014 to HN) and Fundação para a Ciência e Tecnologia (FCT) through individual fellowships (SFRH/BPD/91344/2012 to FC; SFRH/BCC/105888/2014 and SFRH/BPD/112968/2015 to HN) and a FCT research grant (EXPL/BIM-ONC/1656/2013 to HN).
Cancer patients die primarily due to disease recurrence after transient treatment responses. The emergence of therapy-resistant escape variants is fuelled by intra-tumour heterogeneity, underpinned by interference and Darwinian evolution among continuously developing sub-clones in the mutating tumour. Novel cancer cell variants build upon the pre-existing genetic landscape and tumour heterogeneity is often ascribed largely to genetic variability. While mutations are required for cancer development and studies of genetic evolution of tumours have improved our understanding of cancer biology, genetics only represents one dimension of the fitness of each cancer cell. Beyond the mutations, several non-genetic factors also add significant variability, resulting in a complex and highly dynamic tumour cell population that can drive disease under almost any condition. This viewpoint article summarizes the genetic basis of intra-tumour heterogeneity, before dissecting four major interdependent non-genetic factors we think critically contribute to the overall variability of tumour cells in all types of cancer: epigenetic regulation, cellular differentiation hierarchies, gene expression stochasticity and tumour microenvironment. We finally present the relevant technological approaches to address the combined contribution of both genetic and non-genetic factors to intra-tumour heterogeneity, focusing on genomic profiling, cellular lineage tracing and single-cell RNA sequencing technologies. This strategy will ultimately allow dissection of the full range and depth of intra-tumour heterogeneity. We thus believe that understanding how cancer genetics synergize with the emerging non-genetic factors will be key for development of therapies able to tackle tumour escape and thereby improve cancer patient survival.
Cancer patients die primarily due to disease recurrence after transient treatment responses. The emergence of therapy‐resistant escape variants is fuelled by intra‐tumour heterogeneity, underpinned by interference and Darwinian evolution among continuously developing sub‐clones in the mutating tumour. Novel cancer cell variants build upon the pre‐existing genetic landscape and tumour heterogeneity is often ascribed largely to genetic variability. While mutations are required for cancer development and studies of genetic evolution of tumours have improved our understanding of cancer biology, genetics only represents one dimension of the fitness of each cancer cell. Beyond the mutations, several non‐genetic factors also add significant variability, resulting in a complex and highly dynamic tumour cell population that can drive disease under almost any condition. This viewpoint article summarizes the genetic basis of intra‐tumour heterogeneity, before dissecting four major interdependent non‐genetic factors we think critically contribute to the overall variability of tumour cells in all types of cancer: epigenetic regulation, cellular differentiation hierarchies, gene expression stochasticity and tumour microenvironment. We finally present the relevant technological approaches to address the combined contribution of both genetic and non‐genetic factors to intra‐tumour heterogeneity, focusing on genomic profiling, cellular lineage tracing and single‐cell RNA sequencing technologies. This strategy will ultimately allow dissection of the full range and depth of intra‐tumour heterogeneity. We thus believe that understanding how cancer genetics synergize with the emerging non‐genetic factors will be key for development of therapies able to tackle tumour escape and thereby improve cancer patient survival. Intra‐tumour heterogeneity contributes to cancer therapy failure and is ascribed largely to genetic variability between sub‐clones. We discuss the impact of key non‐genetic factors that also underpin intra‐tumour heterogeneity and the technological approaches employed to dissect them. The combined study of both genetic and non‐genetic factors that collectively diversify cancer cell populations represents an important frontier to achieve curative treatments.
Author Norell, Haakan
Caiado, Francisco
Silva-Santos, Bruno
Author_xml – scopusid: 23033354600
  sequence: 1
  givenname: Francisco
  orcidid: 0000-0003-4096-4448
  surname: Caiado
  fullname: Caiado, Francisco
– scopusid: 6505885924
  sequence: 2
  givenname: Bruno
  orcidid: 0000-0003-4141-9302
  surname: Silva-Santos
  fullname: Silva-Santos, Bruno
– scopusid: 12759727600
  sequence: 3
  givenname: Haakan
  orcidid: 0000-0001-5232-7660
  surname: Norell
  fullname: Norell, Haakan
BackLink https://www.ncbi.nlm.nih.gov/pubmed/26945550$$D View this record in MEDLINE/PubMed
BookMark eNqF0MtO3DAUBmCrApVLu-kDVKm6QUihPsd2bLMriJs0Eou2UneW45xMg2aSqZ2A5u1JGIYFC_DGlvX5t85_wHbariXGvgA_gXH9qKlMJyA0Vx_YPmiJuSyU2Xk5y7977CClO86FktZ-ZHtYWKmU4vsMb9o--rwflt0Qs3_UU-zm1FLTr7PTbN417Twrad21VTZd901In9hu7ReJPj_vh-zP5cXv8-t8dnt1c_5zlgepUOVYelnVQAap9IQ1FEID2gqCEYgVlIFQVzXqEAQvdUBrwINFU2jSNXJxyI42uavY_R8o9W7ZpECLhW-pG5IDw00BaKx4n2prNAql9Ei_v6J34-TtOMik7CjQTH8fb1SIXUqRareKzdLHtQPuptLdVLp7Kn3EX58jh3JJ1QvdtjwC2ICHZkHrN6Lc5cXZr23ot82bGLxfuUj3Ter96LhU4KQBrcUjsCOWZQ
CitedBy_id crossref_primary_10_1093_nargab_lqaa062
crossref_primary_10_1021_acsomega_2c06659
crossref_primary_10_15252_embj_2021108389
crossref_primary_10_1007_s12033_023_00777_0
crossref_primary_10_3390_diagnostics11091534
crossref_primary_10_1093_nargab_lqac048
crossref_primary_10_1158_1078_0432_CCR_19_3991
crossref_primary_10_1016_j_semcancer_2018_01_010
crossref_primary_10_1101_gad_300079_117
crossref_primary_10_1016_j_ceb_2021_04_004
crossref_primary_10_1134_S0026893321040051
crossref_primary_10_1016_j_semcancer_2017_08_001
crossref_primary_10_1016_j_semcancer_2017_02_011
crossref_primary_10_1038_s41398_018_0138_2
crossref_primary_10_1002_bies_202000126
crossref_primary_10_1093_evolut_qpad042
crossref_primary_10_1242_dev_181636
crossref_primary_10_1089_omi_2018_0172
crossref_primary_10_1038_s41540_023_00309_1
crossref_primary_10_1080_17474124_2016_1179578
crossref_primary_10_1089_omi_2017_0174
crossref_primary_10_1007_s11934_018_0754_7
crossref_primary_10_1038_s41467_019_12983_z
crossref_primary_10_1016_j_patter_2021_100399
crossref_primary_10_1158_0008_5472_CAN_16_0937
crossref_primary_10_1016_j_omtn_2021_03_017
crossref_primary_10_1038_s41586_018_0024_3
crossref_primary_10_3390_cancers13040615
crossref_primary_10_1089_omi_2020_0185
crossref_primary_10_1016_j_tranon_2017_09_007
crossref_primary_10_1038_s41467_019_08595_2
crossref_primary_10_1038_s41523_021_00363_0
crossref_primary_10_18632_oncotarget_26353
crossref_primary_10_3389_fnetp_2023_1225736
crossref_primary_10_1002_path_6158
crossref_primary_10_1080_17425255_2019_1620731
crossref_primary_10_1038_s41598_017_07851_z
crossref_primary_10_1038_nrc_2016_89
crossref_primary_10_1186_s12943_017_0668_x
crossref_primary_10_1016_j_pan_2018_10_009
crossref_primary_10_1007_s40487_017_0047_1
crossref_primary_10_1111_cup_13119
crossref_primary_10_1186_s13073_020_00741_6
crossref_primary_10_1371_journal_pcbi_1005954
crossref_primary_10_3389_fonc_2022_956738
crossref_primary_10_1371_journal_pcbi_1008702
crossref_primary_10_1158_0008_5472_CAN_21_0482
crossref_primary_10_1016_j_cobme_2021_100348
crossref_primary_10_1111_febs_14365
crossref_primary_10_1097_PGP_0000000000000400
crossref_primary_10_1038_s41587_019_0364_z
crossref_primary_10_3389_fbioe_2022_952726
crossref_primary_10_1007_s00404_017_4292_1
crossref_primary_10_1038_s41598_024_53998_x
crossref_primary_10_1016_j_neo_2019_04_004
Cites_doi 10.1126/science.1235122
10.1038/nm0797-730
10.1016/j.stem.2014.02.006
10.1038/nrg3554
10.1002/emmm.201100209
10.1016/j.ccell.2015.07.012
10.1111/eva.12017
10.1038/nature12344
10.1038/ncomms6871
10.1038/nature10825
10.1016/j.cell.2011.07.026
10.1038/ncomms6901
10.1038/nature09515
10.1038/nature09650
10.1890/10-1245.1
10.1016/j.ccr.2011.08.025
10.1038/nature08781
10.1038/nm.3841
10.1126/scitranslmed.aaa0763
10.1093/jnci/32.6.1201
10.1084/jem.20110105
10.1038/nature10762
10.1038/nature09733
10.1016/j.stem.2011.08.010
10.1371/journal.pbio.1001490
10.1038/nature08489
10.1038/35035005
10.1038/nrmicro1557
10.1038/nature10738
10.1038/nrc3130
10.1016/j.ejca.2013.02.021
10.1038/nmeth.2694
10.1038/nature13556
10.1016/j.ygeno.2014.09.005
10.2105/AJPH.2005.078436
10.1016/j.cell.2015.10.039
10.1016/j.canlet.2012.12.028
10.1038/nature07485
10.1126/science.1216379
10.1016/j.exphem.2014.05.003
10.1038/nature09460
10.1186/gb-2014-15-5-r75
10.1371/journal.pgen.1003972
10.1038/ng1768
10.1038/ng.2891
10.1038/nm.2415
10.1038/nm.3518
10.1146/annurev-pathol-020712-163923
10.1016/j.molcel.2015.05.019
10.1158/1078-0432.CCR-09-2446
10.1534/genetics.106.067678
10.1126/science.1227670
10.1126/science.1160165
10.1101/gad.180331.111
10.1016/j.cell.2013.01.019
10.1126/science.1254257
10.1126/science.959840
10.1056/NEJMoa1113205
10.1016/j.cell.2010.02.027
10.1016/j.stem.2015.05.009
10.1038/nm.3984
10.1126/science.176.4041.1340
10.1016/j.ccell.2014.10.012
10.1073/pnas.1208715109
10.1534/genetics.112.147157
10.1073/pnas.0712345105
10.1056/NEJMoa021967
10.1101/gr.099622.109
10.1073/pnas.1320565110
10.1002/1097-0142(197803)41:3<907::AID-CNCR2820410318>3.0.CO;2-V
10.1016/j.molcel.2014.05.015
10.1038/nm.3522
10.1016/j.ccr.2012.02.022
10.1038/nature09807
10.1371/journal.pgen.1004462
10.1016/j.gde.2013.12.004
10.1016/j.celrep.2014.06.053
10.1200/JCO.2013.50.7921
10.1038/nature15395
10.1158/2159-8290.CD-13-0349
10.1126/science.1064088
10.1038/nature06293
10.1126/science.aab0917
ContentType Journal Article
Copyright 2016 Federation of European Biochemical Societies
2016 Federation of European Biochemical Societies.
Copyright © 2016 Federation of European Biochemical Societies
Copyright_xml – notice: 2016 Federation of European Biochemical Societies
– notice: 2016 Federation of European Biochemical Societies.
– notice: Copyright © 2016 Federation of European Biochemical Societies
DBID RCLKO
CGR
CUY
CVF
ECM
EIF
NPM
AAYXX
CITATION
7QL
7QP
7QR
7TK
7TM
7U9
8FD
C1K
FR3
H94
M7N
P64
RC3
7X8
DOI 10.1111/febs.13705
DatabaseName RCAAP open access repository
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
CrossRef
Bacteriology Abstracts (Microbiology B)
Calcium & Calcified Tissue Abstracts
Chemoreception Abstracts
Neurosciences Abstracts
Nucleic Acids Abstracts
Virology and AIDS Abstracts
Technology Research Database
Environmental Sciences and Pollution Management
Engineering Research Database
AIDS and Cancer Research Abstracts
Algology Mycology and Protozoology Abstracts (Microbiology C)
Biotechnology and BioEngineering Abstracts
Genetics Abstracts
MEDLINE - Academic
DatabaseTitle MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
CrossRef
Virology and AIDS Abstracts
Technology Research Database
Nucleic Acids Abstracts
Neurosciences Abstracts
Biotechnology and BioEngineering Abstracts
Environmental Sciences and Pollution Management
Genetics Abstracts
Bacteriology Abstracts (Microbiology B)
Algology Mycology and Protozoology Abstracts (Microbiology C)
AIDS and Cancer Research Abstracts
Chemoreception Abstracts
Engineering Research Database
Calcium & Calcified Tissue Abstracts
MEDLINE - Academic
DatabaseTitleList Genetics Abstracts
CrossRef

MEDLINE

MEDLINE - Academic
Virology and AIDS Abstracts
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
Discipline Anatomy & Physiology
Chemistry
DissertationSchool Repositório da Universidade de Lisboa
EISSN 1742-4658
EndPage 2258
ExternalDocumentID 4101251291
10_1111_febs_13705
26945550
FEBS13705
10451_48177
Genre reviewArticle
Research Support, Non-U.S. Gov't
Journal Article
Review
GrantInformation_xml – fundername: Associação Portuguesa Contra a Leucemia
– fundername: Fundação para a Ciência e Tecnologia (FCT)
  funderid: SFRH/BPD/91344/2012; SFRH/BCC/105888/2014; SFRH/BPD/112968/2015; EXPL/BIM‐ONC/1656/2013
GroupedDBID ---
-DZ
-~X
.3N
.55
.GA
.Y3
05W
0R~
10A
1OC
24P
29H
31~
33P
36B
3O-
3SF
4.4
50Y
50Z
51W
51X
52M
52N
52O
52P
52R
52S
52T
52U
52V
52W
52X
53G
5GY
5HH
5LA
5RE
5VS
66C
702
7PT
8-0
8-1
8-3
8-4
8-5
8UM
930
A01
A03
A8Z
AAESR
AAEVG
AAHBH
AAHHS
AANLZ
AAONW
AASGY
AAXRX
AAZKR
ABCQN
ABCUV
ABDBF
ABEFU
ABEML
ABPVW
ABQWH
ABXGK
ACAHQ
ACCFJ
ACCZN
ACFBH
ACGFS
ACGOF
ACIWK
ACMXC
ACNCT
ACPOU
ACPRK
ACSCC
ACXBN
ACXQS
ADBBV
ADBTR
ADEOM
ADIZJ
ADKYN
ADMGS
ADOZA
ADXAS
ADZMN
AEEZP
AEGXH
AEIGN
AEIMD
AENEX
AEQDE
AEUQT
AEUYR
AFBPY
AFEBI
AFFPM
AFGKR
AFPWT
AFRAH
AFZJQ
AHBTC
AIACR
AITYG
AIURR
AIWBW
AJBDE
ALAGY
ALMA_UNASSIGNED_HOLDINGS
ALUQN
AMBMR
AMYDB
ATUGU
AZBYB
AZVAB
BAFTC
BAWUL
BFHJK
BHBCM
BMXJE
BROTX
BRXPI
BY8
C1A
C45
CAG
COF
CS3
D-6
D-7
D-E
D-F
DCZOG
DIK
DPXWK
DR2
DRFUL
DRMAN
DRSTM
E3Z
EAD
EAP
EAS
EAU
EBB
EBC
EBD
EBS
EBX
EJD
EMB
EMK
EMOBN
EST
ESTFP
ESX
EX3
F00
F01
F04
F5P
FIJ
FUBAC
G-S
G.N
GODZA
GX1
H.X
HF~
HGLYW
HH5
HZI
HZ~
IHE
IX1
J0M
KBYEO
LATKE
LC2
LC3
LEEKS
LH4
LITHE
LOXES
LP6
LP7
LUTES
LW6
LYRES
MEWTI
MK4
MRFUL
MRMAN
MRSTM
MSFUL
MSMAN
MSSTM
MVM
MXFUL
MXMAN
MXSTM
N04
N05
N9A
NF~
O66
O9-
OBS
OIG
OK1
OVD
P2W
P2X
P2Z
P4B
P4D
PQQKQ
Q.N
Q11
QB0
R.K
RCLKO
RNS
ROL
RX1
SUPJJ
SV3
TEORI
TR2
TUS
UB1
V8K
W8V
W99
WBFHL
WBKPD
WIH
WIJ
WIK
WIN
WOHZO
WOQ
WOW
WQJ
WRC
WXI
WXSBR
WYISQ
X7M
XG1
Y6R
~IA
~KM
~WT
CGR
CUY
CVF
ECM
EIF
NPM
AAYXX
CITATION
7QL
7QP
7QR
7TK
7TM
7U9
8FD
C1K
FR3
H94
M7N
P64
RC3
7X8
ID FETCH-LOGICAL-c4525-2ba4df1e82ebae2f1637129d1c8322d1bce27df27cc30b7c2981a192867e7f203
IEDL.DBID DR2
ISSN 1742-464X
IngestDate Sat Aug 17 00:18:40 EDT 2024
Fri Aug 16 07:56:14 EDT 2024
Thu Oct 10 22:04:27 EDT 2024
Fri Aug 23 03:14:49 EDT 2024
Tue Aug 27 13:56:31 EDT 2024
Sat Aug 24 01:05:55 EDT 2024
Fri Nov 08 15:42:53 EST 2024
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 12
Keywords cancer mutation
single-cell transcriptomics
clonal evolution
leukaemia initiating cells
next-generation sequencing
non-genetic variability
sub-clone
cancer stem cells
lineage tracing
population dynamics
Language English
License 2016 Federation of European Biochemical Societies.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c4525-2ba4df1e82ebae2f1637129d1c8322d1bce27df27cc30b7c2981a192867e7f203
Notes ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-3
content type line 23
ObjectType-Review-1
ObjectType-Article-1
ObjectType-Feature-2
ORCID 0000-0003-4096-4448
0000-0003-4141-9302
0000-0001-5232-7660
OpenAccessLink http://hdl.handle.net/10451/48177
PMID 26945550
PQID 1799573280
PQPubID 28478
PageCount 14
ParticipantIDs proquest_miscellaneous_1808612893
proquest_miscellaneous_1798723557
proquest_journals_1799573280
crossref_primary_10_1111_febs_13705
pubmed_primary_26945550
wiley_primary_10_1111_febs_13705_FEBS13705
rcaap_revistas_10451_48177
PublicationCentury 2000
PublicationDate June 2016
PublicationDateYYYYMMDD 2016-06-01
PublicationDate_xml – month: 06
  year: 2016
  text: June 2016
PublicationDecade 2010
PublicationPlace England
PublicationPlace_xml – name: England
– name: Oxford
PublicationTitle The FEBS journal
PublicationTitleAlternate FEBS J
PublicationYear 2016
Publisher John Wiley & Sons, Inc
Blackwell Publishing Ltd
Publisher_xml – name: John Wiley & Sons, Inc
– name: Blackwell Publishing Ltd
References 2012; 481
2012; 482
2010; 16
2012; 366
1980; 40
2006; 38
2010; 467
2014; 26
2010; 463
2011; 11
2010; 141
2014; 24
1978; 38
2008; 105
2015; 349
2011; 17
2013; 8
1981; 41
1997; 3
1972; 176
2013; 6
2013; 9
2014; 20
2011; 472
2000; 407
2010; 20
2001; 294
2011; 208
2014; 5
2013; 14
2014; 4
1976; 194
2013; 11
2007; 176
2007; 450
1964; 32
2011; 20
2014; 15
2014; 14
2002; 347
2013; 152
2007; 5
2013; 110
2011; 25
2014; 8
2012; 336
2013; 193
2012; 21
2014; 11
2014; 10
2014; 54
2014; 514
2015; 163
2015; 58
2006; 96
2015; 6
2015; 16
2013; 49
2013; 500
2014; 46
2015; 526
2013; 340
2008; 322
1953; 13
2015; 7
2012; 109
2014; 42
2011; 9
2011; 146
2015; 28
2011; 469
2013; 339
1978; 41
2011; 92
2013; 31
2015; 22
2015; 21
1972; 32
2008; 456
2009; 461
2012; 4
2014; 104
2014; 344
e_1_2_13_24_1
e_1_2_13_49_1
e_1_2_13_26_1
e_1_2_13_47_1
e_1_2_13_68_1
e_1_2_13_20_1
e_1_2_13_45_1
e_1_2_13_66_1
e_1_2_13_87_1
Makino S (e_1_2_13_12_1) 1953; 13
e_1_2_13_22_1
e_1_2_13_43_1
e_1_2_13_64_1
e_1_2_13_85_1
e_1_2_13_41_1
e_1_2_13_62_1
e_1_2_13_60_1
e_1_2_13_83_1
e_1_2_13_81_1
e_1_2_13_90_1
e_1_2_13_17_1
Poste G (e_1_2_13_5_1) 1980; 40
e_1_2_13_19_1
e_1_2_13_13_1
e_1_2_13_36_1
e_1_2_13_59_1
e_1_2_13_15_1
e_1_2_13_38_1
e_1_2_13_57_1
e_1_2_13_32_1
e_1_2_13_55_1
e_1_2_13_78_1
Dexter DL (e_1_2_13_3_1) 1978; 38
e_1_2_13_34_1
e_1_2_13_53_1
e_1_2_13_76_1
e_1_2_13_51_1
e_1_2_13_74_1
e_1_2_13_30_1
e_1_2_13_72_1
e_1_2_13_70_1
e_1_2_13_4_1
e_1_2_13_2_1
e_1_2_13_88_1
e_1_2_13_29_1
e_1_2_13_25_1
e_1_2_13_48_1
e_1_2_13_27_1
e_1_2_13_46_1
e_1_2_13_69_1
e_1_2_13_21_1
e_1_2_13_44_1
e_1_2_13_67_1
Shapiro JR (e_1_2_13_8_1) 1981; 41
e_1_2_13_23_1
e_1_2_13_42_1
e_1_2_13_65_1
e_1_2_13_86_1
e_1_2_13_40_1
e_1_2_13_63_1
e_1_2_13_84_1
e_1_2_13_7_1
e_1_2_13_61_1
e_1_2_13_82_1
e_1_2_13_80_1
Danielson KG (e_1_2_13_9_1) 1980; 40
e_1_2_13_91_1
Raz A (e_1_2_13_6_1) 1980; 40
e_1_2_13_18_1
e_1_2_13_39_1
e_1_2_13_14_1
e_1_2_13_35_1
e_1_2_13_16_1
e_1_2_13_37_1
e_1_2_13_58_1
e_1_2_13_79_1
e_1_2_13_10_1
e_1_2_13_31_1
e_1_2_13_56_1
e_1_2_13_77_1
Barranco SC (e_1_2_13_11_1) 1972; 32
e_1_2_13_33_1
e_1_2_13_54_1
e_1_2_13_75_1
e_1_2_13_52_1
e_1_2_13_73_1
e_1_2_13_50_1
e_1_2_13_71_1
e_1_2_13_89_1
e_1_2_13_28_1
References_xml – volume: 461
  start-page: 809
  year: 2009
  end-page: 813
  article-title: Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution
  publication-title: Nature
– volume: 92
  start-page: 1573
  year: 2011
  end-page: 1581
  article-title: Functional and phylogenetic diversity as predictors of biodiversity–ecosystem‐function relationships
  publication-title: Ecology
– volume: 481
  start-page: 506
  year: 2012
  end-page: 510
  article-title: Clonal evolution in relapsed acute myeloid leukaemia revealed by whole‐genome sequencing
  publication-title: Nature
– volume: 208
  start-page: 653
  year: 2011
  end-page: 661
  article-title: Clonal selection in xenografted human T cell acute lymphoblastic leukemia recapitulates gain of malignancy at relapse
  publication-title: J Exp Med
– volume: 46
  start-page: 225
  year: 2014
  end-page: 233
  article-title: Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing
  publication-title: Nat Genet
– volume: 6
  start-page: 5901
  year: 2015
  article-title: Combining gene mutation with gene expression data improves outcome prediction in myelodysplastic syndromes
  publication-title: Nat Commun
– volume: 16
  start-page: 613
  year: 2015
  end-page: 625
  article-title: Epigenetic control of stem cell potential during homeostasis, aging, and disease
  publication-title: Cell Stem Cell
– volume: 467
  start-page: 1109
  year: 2010
  end-page: 1113
  article-title: The patterns and dynamics of genomic instability in metastatic pancreatic cancer
  publication-title: Nature
– volume: 26
  start-page: 813
  year: 2014
  end-page: 825
  article-title: Locally disordered methylation forms the basis of intratumor methylome variation in chronic lymphocytic leukemia
  publication-title: Cancer Cell
– volume: 339
  start-page: 543
  year: 2013
  end-page: 548
  article-title: Variable clonal repopulation dynamics influence chemotherapy response in colorectal cancer
  publication-title: Science
– volume: 96
  start-page: 2104
  year: 2006
  end-page: 2105
  article-title: Rudolf Carl Virchow: medical scientist, social reformer, role model
  publication-title: Am J Public Health
– volume: 20
  start-page: 342
  year: 2014
  end-page: 344
  article-title: Tumor heterogeneity confounds and illuminates: assessing the implications
  publication-title: Nat Med
– volume: 32
  start-page: 2733
  year: 1972
  end-page: 2736
  article-title: Differential sensitivites of human melanoma cells grown in vitro to arabinosylcytosine
  publication-title: Cancer Res
– volume: 8
  start-page: 277
  year: 2013
  end-page: 302
  article-title: Cellular heterogeneity and molecular evolution in cancer
  publication-title: Annu Rev Pathol
– volume: 16
  start-page: 790
  year: 2010
  end-page: 799
  article-title: Prevalence and heterogeneity of KRAS, BRAF, and PIK3CA mutations in primary colorectal adenocarcinomas and their corresponding metastases
  publication-title: Clin Cancer Res
– volume: 347
  start-page: 1999
  year: 2002
  end-page: 2009
  article-title: A gene‐expression signature as a predictor of survival in breast cancer
  publication-title: N Engl J Med
– volume: 41
  start-page: 2349
  year: 1981
  end-page: 2359
  article-title: Isolation, karyotype, and clonal growth of heterogeneous subpopulations of human malignant gliomas
  publication-title: Cancer Res
– volume: 3
  start-page: 730
  year: 1997
  end-page: 737
  article-title: Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell
  publication-title: Nat Med
– volume: 25
  start-page: 2465
  year: 2011
  end-page: 2479
  article-title: Macrophages and cathepsin proteases blunt chemotherapeutic response in breast cancer
  publication-title: Genes Dev
– volume: 40
  start-page: 1636
  year: 1980
  end-page: 1644
  article-title: In vitro selection of murine B16 melanoma variants with enhanced tissue‐invasive properties
  publication-title: Cancer Res
– volume: 104
  start-page: 417
  year: 2014
  end-page: 430
  article-title: Beyond genome sequencing: lineage tracking with barcodes to study the dynamics of evolution, infection, and cancer
  publication-title: Genomics
– volume: 38
  start-page: 468
  year: 2006
  end-page: 473
  article-title: Genetic clonal diversity predicts progression to esophageal adenocarcinoma
  publication-title: Nat Genet
– volume: 336
  start-page: 183
  year: 2012
  end-page: 187
  article-title: Using gene expression noise to understand gene regulation
  publication-title: Science
– volume: 40
  start-page: 1645
  year: 1980
  end-page: 1651
  article-title: Cell surface properties of B16 melanoma variants with differing metastatic potential
  publication-title: Cancer Res
– volume: 15
  start-page: R75
  year: 2014
  article-title: Lentiviral and targeted cellular barcoding reveals ongoing clonal dynamics of cell lines in vitro and in vivo
  publication-title: Genome Biol
– volume: 20
  start-page: 68
  year: 2010
  end-page: 80
  article-title: Inferring tumor progression from genomic heterogeneity
  publication-title: Genome Res
– volume: 6
  start-page: 102
  year: 2013
  end-page: 108
  article-title: Cancer stem cells as “units of selection”
  publication-title: Evol Appl
– volume: 13
  start-page: 1213
  year: 1953
  end-page: 1235
  article-title: Cytological studies of tumors. IX. Characteristic chromosome individuality in tumor strain‐cells in ascites tumors of rats
  publication-title: J Natl Cancer Inst
– volume: 193
  start-page: 565
  year: 2013
  end-page: 585
  article-title: Genetic diversity and the structure of genealogies in rapidly adapting populations
  publication-title: Genetics
– volume: 42
  start-page: 598
  year: 2014
  end-page: 608
  article-title: Cellular barcoding: a technical appraisal
  publication-title: Exp Hematol
– volume: 9
  start-page: 357
  year: 2011
  end-page: 365
  article-title: Distinct types of tumor‐initiating cells form human colon cancer tumors and metastases
  publication-title: Cell Stem Cell
– volume: 467
  start-page: 1114
  year: 2010
  end-page: 1117
  article-title: Distant metastasis occurs late during the genetic evolution of pancreatic cancer
  publication-title: Nature
– volume: 450
  start-page: 56
  year: 2007
  end-page: 62
  article-title: Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system
  publication-title: Nature
– volume: 163
  start-page: 799
  year: 2015
  end-page: 810
  article-title: Design and analysis of single‐cell sequencing experiments
  publication-title: Cell
– volume: 514
  start-page: 54
  year: 2014
  end-page: 58
  article-title: Non‐cell‐autonomous driving of tumour growth supports sub‐clonal heterogeneity
  publication-title: Nature
– volume: 469
  start-page: 362
  year: 2011
  end-page: 367
  article-title: Evolution of human BCR‐ABL1 lymphoblastic leukaemia‐initiating cells
  publication-title: Nature
– volume: 339
  start-page: 1546
  year: 2013
  end-page: 1558
  article-title: Cancer genome landscapes
  publication-title: Science
– volume: 366
  start-page: 883
  year: 2012
  end-page: 892
  article-title: Intratumor heterogeneity and branched evolution revealed by multiregion sequencing
  publication-title: N Engl J Med
– volume: 58
  start-page: 563
  year: 2015
  end-page: 564
  article-title: Single‐cell transcriptomics enters the age of mass production
  publication-title: Mol Cell
– volume: 11
  start-page: 726
  year: 2011
  end-page: 734
  article-title: A decade of exploring the cancer epigenome – biological and translational implications
  publication-title: Nat Rev Cancer
– volume: 49
  start-page: 2000
  year: 2013
  end-page: 2009
  article-title: Cancer gene expression signatures – the rise and fall?
  publication-title: Eur J Cancer
– volume: 22
  start-page: 105
  year: 2015
  end-page: 113
  article-title: Pan‐cancer analysis of the extent and consequences of intratumor heterogeneity
  publication-title: Nat Med
– volume: 38
  start-page: 3174
  year: 1978
  end-page: 3181
  article-title: Heterogeneity of tumor cells from a single mouse mammary tumor
  publication-title: Cancer Res
– volume: 152
  start-page: 714
  year: 2013
  end-page: 726
  article-title: Evolution and impact of subclonal mutations in chronic lymphocytic leukemia
  publication-title: Cell
– volume: 176
  start-page: 1759
  year: 2007
  end-page: 1798
  article-title: Beneficial mutation selection balance and the effect of linkage on positive selection
  publication-title: Genetics
– volume: 24
  start-page: 82
  year: 2014
  end-page: 91
  article-title: Single cell analysis of cancer genomes
  publication-title: Curr Opin Genet Dev
– volume: 40
  start-page: 1812
  year: 1980
  end-page: 1819
  article-title: Selection and characterization in culture of mammary tumor cells with distinctive growth properties in vivo
  publication-title: Cancer Res
– volume: 28
  start-page: 307
  year: 2015
  end-page: 317
  article-title: DNA methylation and somatic mutations converge on the cell cycle and define similar evolutionary histories in brain tumors
  publication-title: Cancer Cell
– volume: 17
  start-page: 1086
  year: 2011
  end-page: 1093
  article-title: Stem cell gene expression programs influence clinical outcome in human leukemia
  publication-title: Nat Med
– volume: 20
  start-page: 538
  year: 2011
  end-page: 549
  article-title: Macrophage binding to receptor VCAM‐1 transmits survival signals in breast cancer cells that invade the lungs
  publication-title: Cancer Cell
– volume: 14
  start-page: 765
  year: 2013
  end-page: 780
  article-title: Mutations in regulators of the epigenome and their connections to global chromatin patterns in cancer
  publication-title: Nat Rev Genet
– volume: 500
  start-page: 571
  year: 2013
  end-page: 574
  article-title: Pervasive genetic hitchhiking and clonal interference in forty evolving yeast populations
  publication-title: Nature
– volume: 469
  start-page: 356
  year: 2011
  end-page: 361
  article-title: Genetic variegation of clonal architecture and propagating cells in leukaemia
  publication-title: Nature
– volume: 20
  start-page: 344
  year: 2014
  end-page: 346
  article-title: Tumor heterogeneity confounds and illuminates: a case for Darwinian tumor evolution
  publication-title: Nat Med
– volume: 5
  start-page: 48
  year: 2007
  end-page: 56
  article-title: Persister cells, dormancy and infectious disease
  publication-title: Nat Rev Microbiol
– volume: 11
  start-page: 41
  year: 2014
  end-page: 46
  article-title: Quantitative assessment of single‐cell RNA‐sequencing methods
  publication-title: Nat Methods
– volume: 141
  start-page: 69
  year: 2010
  end-page: 80
  article-title: A chromatin‐mediated reversible drug‐tolerant state in cancer cell subpopulations
  publication-title: Cell
– volume: 14
  start-page: 275
  year: 2014
  end-page: 291
  article-title: Evolution of the cancer stem cell model
  publication-title: Cell Stem Cell
– volume: 7
  start-page: 281re2
  year: 2015
  article-title: Single‐cell genotyping demonstrates complex clonal diversity in acute myeloid leukemia
  publication-title: Sci Transl Med
– volume: 31
  start-page: 3898
  year: 2013
  end-page: 3905
  article-title: Clonal heterogeneity as detected by metaphase karyotyping is an indicator of poor prognosis in acute myeloid leukemia
  publication-title: J Clin Oncol
– volume: 194
  start-page: 23
  year: 1976
  end-page: 28
  article-title: The clonal evolution of tumor cell populations
  publication-title: Science
– volume: 344
  start-page: 1396
  year: 2014
  end-page: 1401
  article-title: Single‐cell RNA‐seq highlights intratumoral heterogeneity in primary glioblastoma
  publication-title: Science
– volume: 4
  start-page: 143
  year: 2012
  end-page: 159
  article-title: MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review
  publication-title: EMBO Mol Med
– volume: 41
  start-page: 907
  year: 1978
  end-page: 911
  article-title: Immunofluorescent detection of estrogen receptors in breast cancer. Comparison with dextran‐coated charcoal and sucrose gradient assays
  publication-title: Cancer
– volume: 526
  start-page: 525
  year: 2015
  end-page: 530
  article-title: Mutations driving CLL and their evolution in progression and relapse
  publication-title: Nature
– volume: 21
  start-page: 309
  year: 2012
  end-page: 322
  article-title: Accessories to the crime: functions of cells recruited to the tumor microenvironment
  publication-title: Cancer Cell
– volume: 110
  start-page: 20111
  year: 2013
  end-page: 20116
  article-title: Prostate cancer originating in basal cells progresses to adenocarcinoma propagated by luminal‐like cells
  publication-title: Proc Natl Acad Sci U S A
– volume: 5
  start-page: 5871
  year: 2014
  article-title: DNA barcoding reveals diverse growth kinetics of human breast tumour subclones in serially passaged xenografts
  publication-title: Nat Commun
– volume: 456
  start-page: 66
  year: 2008
  end-page: 72
  article-title: DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome
  publication-title: Nature
– volume: 32
  start-page: 1201
  year: 1964
  end-page: 1210
  article-title: Relationship between growth rate and differentiation of melanoma in vivo
  publication-title: J Natl Cancer Inst
– volume: 105
  start-page: 4283
  year: 2008
  end-page: 4288
  article-title: Comparative lesion sequencing provides insights into tumor evolution
  publication-title: Proc Natl Acad Sci U S A
– volume: 11
  start-page: e1001490
  year: 2013
  article-title: Parallel evolutionary dynamics of adaptive diversification in
  publication-title: PLoS Biol
– volume: 322
  start-page: 1511
  year: 2008
  end-page: 1516
  article-title: Dynamic proteomics of individual cancer cells in response to a drug
  publication-title: Science
– volume: 109
  start-page: 14508
  year: 2012
  end-page: 14513
  article-title: Detection of ultra‐rare mutations by next‐generation sequencing
  publication-title: Proc Natl Acad Sci U S A
– volume: 146
  start-page: 633
  year: 2011
  end-page: 644
  article-title: Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells
  publication-title: Cell
– volume: 4
  start-page: 348
  year: 2014
  end-page: 361
  article-title: Evolution of DNA methylation is linked to genetic aberrations in chronic lymphocytic leukemia
  publication-title: Cancer Discov
– volume: 349
  start-page: 1351
  year: 2015
  end-page: 1356
  article-title: RNA‐Seq of single prostate CTCs implicates noncanonical Wnt signaling in antiandrogen resistance
  publication-title: Science (80‐.)
– volume: 482
  start-page: 529
  year: 2012
  end-page: 533
  article-title: Clonal selection drives genetic divergence of metastatic medulloblastoma
  publication-title: Nature
– volume: 9
  start-page: e1003972
  year: 2013
  article-title: Whole genome, whole population sequencing reveals that loss of signaling networks is the major adaptive strategy in a constant environment
  publication-title: PLoS Genet
– volume: 8
  start-page: 798
  year: 2014
  end-page: 806
  article-title: Intratumor DNA methylation heterogeneity reflects clonal evolution in aggressive prostate cancer
  publication-title: Cell Rep
– volume: 463
  start-page: 913
  year: 2010
  end-page: 918
  article-title: Variability in gene expression underlies incomplete penetrance
  publication-title: Nature
– volume: 21
  start-page: 440
  year: 2015
  end-page: 448
  article-title: Studying clonal dynamics in response to cancer therapy using high‐complexity barcoding
  publication-title: Nat Med
– volume: 472
  start-page: 90
  year: 2011
  end-page: 94
  article-title: Tumour evolution inferred by single‐cell sequencing
  publication-title: Nature
– volume: 10
  start-page: e1004462
  year: 2014
  article-title: Clonal architecture of secondary acute myeloid leukemia defined by single‐cell sequencing
  publication-title: PLoS Genet
– volume: 54
  start-page: 716
  year: 2014
  end-page: 727
  article-title: Cancer epigenetics: tumor heterogeneity, plasticity of stem‐like states, and drug resistance
  publication-title: Mol Cell
– volume: 176
  start-page: 1340
  year: 1972
  end-page: 1341
  article-title: Tumor etiology and chromosome pattern
  publication-title: Science
– volume: 294
  start-page: 804
  year: 2001
  end-page: 808
  article-title: Biodiversity and ecosystem functioning: current knowledge and future challenges
  publication-title: Science
– volume: 481
  start-page: 306
  year: 2012
  end-page: 313
  article-title: Clonal evolution in cancer
  publication-title: Nature
– volume: 407
  start-page: 477
  year: 2000
  end-page: 483
  article-title: A yeast prion provides a mechanism for genetic variation and phenotypic diversity
  publication-title: Nature
– volume: 340
  start-page: 212
  year: 2013
  end-page: 219
  article-title: Advances for studying clonal evolution in cancer
  publication-title: Cancer Lett
– ident: e_1_2_13_55_1
  doi: 10.1126/science.1235122
– ident: e_1_2_13_62_1
  doi: 10.1038/nm0797-730
– ident: e_1_2_13_63_1
  doi: 10.1016/j.stem.2014.02.006
– ident: e_1_2_13_56_1
  doi: 10.1038/nrg3554
– ident: e_1_2_13_53_1
  doi: 10.1002/emmm.201100209
– ident: e_1_2_13_60_1
  doi: 10.1016/j.ccell.2015.07.012
– ident: e_1_2_13_67_1
  doi: 10.1111/eva.12017
– ident: e_1_2_13_40_1
  doi: 10.1038/nature12344
– ident: e_1_2_13_82_1
  doi: 10.1038/ncomms6871
– ident: e_1_2_13_22_1
  doi: 10.1038/nature10825
– ident: e_1_2_13_64_1
  doi: 10.1016/j.cell.2011.07.026
– ident: e_1_2_13_87_1
  doi: 10.1038/ncomms6901
– ident: e_1_2_13_20_1
  doi: 10.1038/nature09515
– ident: e_1_2_13_68_1
  doi: 10.1038/nature09650
– ident: e_1_2_13_47_1
  doi: 10.1890/10-1245.1
– ident: e_1_2_13_75_1
  doi: 10.1016/j.ccr.2011.08.025
– ident: e_1_2_13_72_1
  doi: 10.1038/nature08781
– ident: e_1_2_13_84_1
  doi: 10.1038/nm.3841
– ident: e_1_2_13_33_1
  doi: 10.1126/scitranslmed.aaa0763
– ident: e_1_2_13_10_1
  doi: 10.1093/jnci/32.6.1201
– ident: e_1_2_13_69_1
  doi: 10.1084/jem.20110105
– ident: e_1_2_13_32_1
  doi: 10.1038/nature10762
– ident: e_1_2_13_70_1
  doi: 10.1038/nature09733
– ident: e_1_2_13_80_1
  doi: 10.1016/j.stem.2011.08.010
– ident: e_1_2_13_39_1
  doi: 10.1371/journal.pbio.1001490
– volume: 40
  start-page: 1812
  year: 1980
  ident: e_1_2_13_9_1
  article-title: Selection and characterization in culture of mammary tumor cells with distinctive growth properties in vivo
  publication-title: Cancer Res
  contributor:
    fullname: Danielson KG
– ident: e_1_2_13_19_1
  doi: 10.1038/nature08489
– ident: e_1_2_13_48_1
  doi: 10.1038/35035005
– ident: e_1_2_13_49_1
  doi: 10.1038/nrmicro1557
– ident: e_1_2_13_31_1
  doi: 10.1038/nature10738
– ident: e_1_2_13_52_1
  doi: 10.1038/nrc3130
– ident: e_1_2_13_85_1
  doi: 10.1016/j.ejca.2013.02.021
– ident: e_1_2_13_88_1
  doi: 10.1038/nmeth.2694
– ident: e_1_2_13_37_1
  doi: 10.1038/nature13556
– ident: e_1_2_13_78_1
  doi: 10.1016/j.ygeno.2014.09.005
– ident: e_1_2_13_2_1
  doi: 10.2105/AJPH.2005.078436
– ident: e_1_2_13_44_1
  doi: 10.1016/j.cell.2015.10.039
– ident: e_1_2_13_42_1
  doi: 10.1016/j.canlet.2012.12.028
– ident: e_1_2_13_14_1
  doi: 10.1038/nature07485
– ident: e_1_2_13_71_1
  doi: 10.1126/science.1216379
– ident: e_1_2_13_79_1
  doi: 10.1016/j.exphem.2014.05.003
– ident: e_1_2_13_21_1
  doi: 10.1038/nature09460
– ident: e_1_2_13_83_1
  doi: 10.1186/gb-2014-15-5-r75
– ident: e_1_2_13_38_1
  doi: 10.1371/journal.pgen.1003972
– ident: e_1_2_13_25_1
  doi: 10.1038/ng1768
– volume: 38
  start-page: 3174
  year: 1978
  ident: e_1_2_13_3_1
  article-title: Heterogeneity of tumor cells from a single mouse mammary tumor
  publication-title: Cancer Res
  contributor:
    fullname: Dexter DL
– volume: 40
  start-page: 1636
  year: 1980
  ident: e_1_2_13_5_1
  article-title: In vitro selection of murine B16 melanoma variants with enhanced tissue‐invasive properties
  publication-title: Cancer Res
  contributor:
    fullname: Poste G
– ident: e_1_2_13_16_1
  doi: 10.1038/ng.2891
– ident: e_1_2_13_65_1
  doi: 10.1038/nm.2415
– ident: e_1_2_13_15_1
  doi: 10.1038/nm.3518
– ident: e_1_2_13_51_1
  doi: 10.1146/annurev-pathol-020712-163923
– ident: e_1_2_13_91_1
  doi: 10.1016/j.molcel.2015.05.019
– ident: e_1_2_13_18_1
  doi: 10.1158/1078-0432.CCR-09-2446
– ident: e_1_2_13_36_1
  doi: 10.1534/genetics.106.067678
– ident: e_1_2_13_50_1
  doi: 10.1126/science.1227670
– ident: e_1_2_13_73_1
  doi: 10.1126/science.1160165
– ident: e_1_2_13_76_1
  doi: 10.1101/gad.180331.111
– ident: e_1_2_13_28_1
  doi: 10.1016/j.cell.2013.01.019
– ident: e_1_2_13_89_1
  doi: 10.1126/science.1254257
– volume: 40
  start-page: 1645
  year: 1980
  ident: e_1_2_13_6_1
  article-title: Cell surface properties of B16 melanoma variants with differing metastatic potential
  publication-title: Cancer Res
  contributor:
    fullname: Raz A
– ident: e_1_2_13_13_1
  doi: 10.1126/science.959840
– ident: e_1_2_13_17_1
  doi: 10.1056/NEJMoa1113205
– ident: e_1_2_13_61_1
  doi: 10.1016/j.cell.2010.02.027
– ident: e_1_2_13_66_1
  doi: 10.1016/j.stem.2015.05.009
– ident: e_1_2_13_30_1
  doi: 10.1038/nm.3984
– ident: e_1_2_13_7_1
  doi: 10.1126/science.176.4041.1340
– ident: e_1_2_13_57_1
  doi: 10.1016/j.ccell.2014.10.012
– ident: e_1_2_13_41_1
  doi: 10.1073/pnas.1208715109
– ident: e_1_2_13_35_1
  doi: 10.1534/genetics.112.147157
– volume: 32
  start-page: 2733
  year: 1972
  ident: e_1_2_13_11_1
  article-title: Differential sensitivites of human melanoma cells grown in vitro to arabinosylcytosine
  publication-title: Cancer Res
  contributor:
    fullname: Barranco SC
– ident: e_1_2_13_45_1
  doi: 10.1073/pnas.0712345105
– ident: e_1_2_13_86_1
  doi: 10.1056/NEJMoa021967
– ident: e_1_2_13_24_1
  doi: 10.1101/gr.099622.109
– ident: e_1_2_13_81_1
  doi: 10.1073/pnas.1320565110
– ident: e_1_2_13_4_1
  doi: 10.1002/1097-0142(197803)41:3<907::AID-CNCR2820410318>3.0.CO;2-V
– ident: e_1_2_13_54_1
  doi: 10.1016/j.molcel.2014.05.015
– ident: e_1_2_13_29_1
  doi: 10.1038/nm.3522
– ident: e_1_2_13_74_1
  doi: 10.1016/j.ccr.2012.02.022
– ident: e_1_2_13_23_1
  doi: 10.1038/nature09807
– ident: e_1_2_13_34_1
  doi: 10.1371/journal.pgen.1004462
– ident: e_1_2_13_43_1
  doi: 10.1016/j.gde.2013.12.004
– ident: e_1_2_13_59_1
  doi: 10.1016/j.celrep.2014.06.053
– volume: 41
  start-page: 2349
  year: 1981
  ident: e_1_2_13_8_1
  article-title: Isolation, karyotype, and clonal growth of heterogeneous subpopulations of human malignant gliomas
  publication-title: Cancer Res
  contributor:
    fullname: Shapiro JR
– ident: e_1_2_13_26_1
  doi: 10.1200/JCO.2013.50.7921
– ident: e_1_2_13_27_1
  doi: 10.1038/nature15395
– ident: e_1_2_13_58_1
  doi: 10.1158/2159-8290.CD-13-0349
– volume: 13
  start-page: 1213
  year: 1953
  ident: e_1_2_13_12_1
  article-title: Cytological studies of tumors. IX. Characteristic chromosome individuality in tumor strain‐cells in ascites tumors of rats
  publication-title: J Natl Cancer Inst
  contributor:
    fullname: Makino S
– ident: e_1_2_13_46_1
  doi: 10.1126/science.1064088
– ident: e_1_2_13_77_1
  doi: 10.1038/nature06293
– ident: e_1_2_13_90_1
  doi: 10.1126/science.aab0917
SSID ssj0035499
Score 2.4781783
SecondaryResourceType review_article
Snippet © 2016 Federation of European Biochemical Societies Cancer patients die primarily due to disease recurrence after transient treatment responses. The emergence...
Cancer patients die primarily due to disease recurrence after transient treatment responses. The emergence of therapy‐resistant escape variants is fuelled by...
Cancer patients die primarily due to disease recurrence after transient treatment responses. The emergence of therapy-resistant escape variants is fuelled by...
SourceID proquest
crossref
pubmed
wiley
rcaap
SourceType Aggregation Database
Index Database
Publisher
StartPage 2245
SubjectTerms Cancer
Cancer mutation
Cancer stem cells
Cell Lineage - genetics
Clonal evolution
Epigenesis, Genetic
Evolution & development
Evolution, Molecular
Gene expression
Gene Expression Regulation, Neoplastic
Genetic Fitness
Genetic Heterogeneity
Genetics
Humans
Leukaemia initiating cells
Lineage tracing
Mutation
Neoplasms - genetics
Neoplasms - pathology
next‐generation sequencing
non‐genetic variability
Population dynamics
single‐cell transcriptomics
sub‐clone
Tumor Microenvironment - genetics
Title Intra-tumour heterogeneity : going beyond genetics
URI http://hdl.handle.net/10451/48177
https://onlinelibrary.wiley.com/doi/abs/10.1111%2Ffebs.13705
https://www.ncbi.nlm.nih.gov/pubmed/26945550
https://www.proquest.com/docview/1799573280
https://search.proquest.com/docview/1798723557
https://search.proquest.com/docview/1808612893
Volume 283
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1LSwMxEB7Ei158P7ZWiSgehC3dbLrZghdfRQU9-IBeZEmyWQVxK7U96MmfIPgP-0ucyXbrCwQ97UIeJJlJ8k0y8wVgU8QqM01N518oBsEt93WKutwUXOk401a7G_zTs-joSpy0G-0x2CljYQp-iNGBG80Mt17TBFf68dMkz6x-rAWhdASm-CV_roPzEXdUSIZPEQ3JfRGJ9pCblNx4Pop-3Y1-QExErF2j1MNX5Oq2ntY0XJeNLjxO7mr9nq6Z5298jv_t1QxMDTEp2y2UaBbGbD4H87s52uP3T2yLOS9Rd_w-BxP75Qtx8xAd08nw4OW117_HOtgtudZ0UCMtQns2eHljNx3cGZl2UTKMEogUegGuWoeX-0f-8B0G39Ctp8-1EmkW2JhbrSzPEMJJhAlpYGg5SANtLJdpxqUxYV1Lw5txoBA5xpG0MuP1cBHG805ul4HplNhwQisUws66xZyKQJdtEBG9NqkHG6U8koeCbiMpzRQamsQNjQfVUlTJcMphClHbEfVQ3YP1UTKOCN2AqNx2-i5PLDlCLPlLnhitPNy1m6EHS4UajJpCYb8NtOk8qDi9SMgVG1E8liKenkTEgcSqt52Ef-lA0jrcu3B_lb9kXoFJxGtR4alWhfFet29XERP19JrT_XeQyQZE
link.rule.ids 315,783,787,1378,27936,27937,46306,46730
linkProvider Wiley-Blackwell
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3JTsMwEB0hOMCFfQmrEYgDUqrGceP0yFaV9cAi9RbZjgMSaoqgPcCJT0DiD_kSZpy0bBIS3CJ5UeyZsd-Mx88AmyJWmalrin-hGAS33Ncp6nJdcKXjTFvtTvBPz6LmlThq1Vplbg7dhSn4IQYBN7IMt16TgVNA-pOVZ1Y_VIJQEoPpCNp7SC837J8P2KNCcn2K-5DcF5FoleyklMjz0fbrfvQDZCJmvTdK3X3Frm7zaUwUL6w-OM5Cyjm5rfS6umKevjE6_ntckzBewlK2U-jRFAzZfBpmdnJ0yduPbIu5RFEXgZ-G0b3-I3EzEB1ScPjt-aXba2Mf7IayazqolBbRPXt7fmXXHdwcmXYXZRgVEC_0LFw1Di73mn75FINv6ODT51qJNAtszK1WlmeI4iQihTQwtCKkgTaWyzTj0piwqqXh9ThQCB7jSFqZ8Wo4B8N5J7cLwHRKhDihFQqRZ9ViTUW4y9aIi16b1IONvkCSu4JxI-l7KjQ1iZsaD5b7skpKq8MSYrcj9qGqB-uDYpwROgRRue30XJ1YckRZ8pc6MTp6uHHXQw_mCz0Y_Ard_K2hW-fBolOMhLKxEchjK6LqSUQcSOx624n4lwEkjYPdC_e1-JfKazDavDw9SU4Oz46XYAzhW1Qkri3DcPe-Z1cQInX1qjOEd-E6Clw
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1LaxsxEB6CA2kvTWP3sXlVoaWHwppdrbxaQy9uYhMnbShtDb6URdJqGwhZm8Q-JKf8hEL_oX9JZ7ReN27B0NwW9ECrmdF8I40-AbwRicpNW9P-F4pBcMt9naEutwVXOsm11e4E_9NZfDwQJ8PWcA3eV3dhSn6IxYYbWYZbr8nAx1l-z8hzq6-bYSSJwHRdxAh9CRJ9WZBHRRT5lNchuS9iMZyTk1Iez5-2y-7oH4yJkPXKKDVehq7O9_Q24Xs16jLl5KI5neimuf2L0PGhv_UUnsxBKeuUWrQFa7aoQ6NTYEB-ecPeMpcm6vbf6_DosHoirgFxn7aGZ3c_J9NL7IOdU27NCFXSIrZns7tf7McIXSPT7poMowJihX4Gg1732-GxP3-IwTd07OlzrUSWhzbhVivLc8RwEnFCFhpaD7JQG8tllnNpTBRoaXg7CRVCxySWVuY8iJ5DrRgV9iUwnREdTmSFQtwZWKypCHXZFjHRa5N58LqSRzou-TbSKk6hqUnd1HiwW4kqndsclhC3HXEPBR4cLIpxRugIRBV2NHV1EskRY8kVdRIM89BttyMPXpRqsBgK3fttYVDnwbbTi5RysRHGYysi6klFEkrs-p2T8IofSHvdD1_d1_b_VH4FG5-PeunH_tnpDjxG7BaXWWu7UJtcTe0e4qOJ3ndm8Bu8lQkL
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Intra-tumour+heterogeneity+-+going+beyond+genetics&rft.jtitle=The+FEBS+journal&rft.au=Caiado%2C+Francisco&rft.au=Silva-Santos%2C+Bruno&rft.au=Norell%2C+H%C3%A5kan&rft.date=2016-06-01&rft.eissn=1742-4658&rft.volume=283&rft.issue=12&rft.spage=2245&rft_id=info:doi/10.1111%2Ffebs.13705&rft_id=info%3Apmid%2F26945550&rft.externalDocID=26945550
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1742-464X&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1742-464X&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1742-464X&client=summon