Abstract 2560: Werner syndrome helicase is a selective vulnerability of microsatellite instability-high tumor cells

Targeted cancer therapy is based on exploiting selective dependencies of tumor cells. By leveraging recent large-scale genomic profiling and functional screening of cancer cell lines we identified Werner syndrome helicase (WRN) as a novel specific vulnerability of microsatellite instability-high (MS...

Full description

Saved in:
Bibliographic Details
Published inCancer research (Chicago, Ill.) Vol. 79; no. 13_Supplement; p. 2560
Main Authors Lieb, Simone, Blaha-Ostermann, Silvia, Kamper, Elisabeth, Ehrenhöfer-Wölfer, Katharina, Schlattl, Andreas, Wernitznig, Andreas, Lipp, Jesse, Nagasaka, Kota, Bader, Gerd, Neumueller, Ralph, Kraut, Norbert, Pearson, Mark, Woehrle, Simon, Petronczki, Mark
Format Journal Article
LanguageEnglish
Published 01.07.2019
Online AccessGet full text

Cover

Loading…
Abstract Targeted cancer therapy is based on exploiting selective dependencies of tumor cells. By leveraging recent large-scale genomic profiling and functional screening of cancer cell lines we identified Werner syndrome helicase (WRN) as a novel specific vulnerability of microsatellite instability-high (MSI-H) cancer cells. MSI, caused by defective mismatch repair is frequently detected in human malignancies, in particular in colorectal, endometrial and gastric cancers. We demonstrate that WRN inactivation selectively impairs the viability of MSI-H but not microsatellite stable (MSS) colorectal and endometrial cancer cell lines. In MSI-H cells, WRN loss results in the emergence of chromosome breaks, chromatin bridges and micronuclei highlighting defective genome integrity. WRN variants harboring mutations abrogating the ATPase function of WRN helicase fail to rescue the viability phenotype of WRN-depleted MSI-H colorectal cells. Our study suggests that pharmacological inhibition of WRN helicase function might represent a novel opportunity to develop a targeted therapy for MSI-H cancers. Citation Format: Simone Lieb, Silvia Blaha-Ostermann, Elisabeth Kamper, Katharina Ehrenhöfer-Wölfer, Andreas Schlattl, Andreas Wernitznig, Jesse Lipp, Kota Nagasaka, Gerd Bader, Ralph Neumueller, Norbert Kraut, Mark Pearson, Simon Woehrle, Mark Petronczki. Werner syndrome helicase is a selective vulnerability of microsatellite instability-high tumor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2560.
AbstractList Targeted cancer therapy is based on exploiting selective dependencies of tumor cells. By leveraging recent large-scale genomic profiling and functional screening of cancer cell lines we identified Werner syndrome helicase (WRN) as a novel specific vulnerability of microsatellite instability-high (MSI-H) cancer cells. MSI, caused by defective mismatch repair is frequently detected in human malignancies, in particular in colorectal, endometrial and gastric cancers. We demonstrate that WRN inactivation selectively impairs the viability of MSI-H but not microsatellite stable (MSS) colorectal and endometrial cancer cell lines. In MSI-H cells, WRN loss results in the emergence of chromosome breaks, chromatin bridges and micronuclei highlighting defective genome integrity. WRN variants harboring mutations abrogating the ATPase function of WRN helicase fail to rescue the viability phenotype of WRN-depleted MSI-H colorectal cells. Our study suggests that pharmacological inhibition of WRN helicase function might represent a novel opportunity to develop a targeted therapy for MSI-H cancers. Citation Format: Simone Lieb, Silvia Blaha-Ostermann, Elisabeth Kamper, Katharina Ehrenhöfer-Wölfer, Andreas Schlattl, Andreas Wernitznig, Jesse Lipp, Kota Nagasaka, Gerd Bader, Ralph Neumueller, Norbert Kraut, Mark Pearson, Simon Woehrle, Mark Petronczki. Werner syndrome helicase is a selective vulnerability of microsatellite instability-high tumor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2560.
Author Pearson, Mark
Kamper, Elisabeth
Nagasaka, Kota
Bader, Gerd
Blaha-Ostermann, Silvia
Neumueller, Ralph
Wernitznig, Andreas
Lipp, Jesse
Lieb, Simone
Schlattl, Andreas
Ehrenhöfer-Wölfer, Katharina
Kraut, Norbert
Woehrle, Simon
Petronczki, Mark
Author_xml – sequence: 1
  givenname: Simone
  surname: Lieb
  fullname: Lieb, Simone
– sequence: 2
  givenname: Silvia
  surname: Blaha-Ostermann
  fullname: Blaha-Ostermann, Silvia
– sequence: 3
  givenname: Elisabeth
  surname: Kamper
  fullname: Kamper, Elisabeth
– sequence: 4
  givenname: Katharina
  surname: Ehrenhöfer-Wölfer
  fullname: Ehrenhöfer-Wölfer, Katharina
– sequence: 5
  givenname: Andreas
  surname: Schlattl
  fullname: Schlattl, Andreas
– sequence: 6
  givenname: Andreas
  surname: Wernitznig
  fullname: Wernitznig, Andreas
– sequence: 7
  givenname: Jesse
  surname: Lipp
  fullname: Lipp, Jesse
– sequence: 8
  givenname: Kota
  surname: Nagasaka
  fullname: Nagasaka, Kota
– sequence: 9
  givenname: Gerd
  surname: Bader
  fullname: Bader, Gerd
– sequence: 10
  givenname: Ralph
  surname: Neumueller
  fullname: Neumueller, Ralph
– sequence: 11
  givenname: Norbert
  surname: Kraut
  fullname: Kraut, Norbert
– sequence: 12
  givenname: Mark
  surname: Pearson
  fullname: Pearson, Mark
– sequence: 13
  givenname: Simon
  surname: Woehrle
  fullname: Woehrle, Simon
– sequence: 14
  givenname: Mark
  surname: Petronczki
  fullname: Petronczki, Mark
BookMark eNqdj81KAzEQx4NUcGt9BGFeIDXZbuzqrYjixZvgMaTprBvJJpJJC_v2Jlh8AE_D_D-G-S3ZIsSAjN1KsZZS9XdSbXq-7Tq13r21Qj7wVt2LC9b86QvWCCF6rrpte8WWRF9lVVKohtFuTzkZm6GWHuEDU8AENIdDihPCiN5ZQwiOwAChR5vdCeF09CVn9s67PEMcYHI2RTIZfVFKPFA-u3x0nyPk4xQT2GLTil0OxhPenOc1Uy_P70-vvF6ghIP-Tm4yadZS6EqoK4muJPqXUNdnN__t_QBvll31
ContentType Journal Article
DBID AAYXX
CITATION
DOI 10.1158/1538-7445.AM2019-2560
DatabaseName CrossRef
DatabaseTitle CrossRef
DatabaseTitleList CrossRef
DeliveryMethod fulltext_linktorsrc
Discipline Medicine
EISSN 1538-7445
EndPage 2560
ExternalDocumentID 10_1158_1538_7445_AM2019_2560
GroupedDBID ---
-ET
18M
29B
2WC
34G
39C
476
53G
5GY
5RE
5VS
6J9
AAYXX
ABOCM
ACGFO
ACIWK
ACPRK
ACSVP
ADBBV
ADCOW
ADNWM
AENEX
AFHIN
AFOSN
AFRAH
ALMA_UNASSIGNED_HOLDINGS
BAWUL
BTFSW
CITATION
CS3
DIK
DU5
EBS
EJD
F5P
FRP
GX1
H13
IH2
KQ8
L7B
LSO
OK1
P0W
P2P
PQQKQ
RCR
RHF
RHI
RNS
SJN
TR2
W2D
W8F
WH7
WOQ
YKV
YZZ
ID FETCH-crossref_primary_10_1158_1538_7445_AM2019_25603
ISSN 0008-5472
IngestDate Thu Nov 21 23:17:33 EST 2024
IsPeerReviewed true
IsScholarly true
Issue 13_Supplement
Language English
LinkModel OpenURL
MergedId FETCHMERGED-crossref_primary_10_1158_1538_7445_AM2019_25603
ParticipantIDs crossref_primary_10_1158_1538_7445_AM2019_2560
PublicationCentury 2000
PublicationDate 2019-07-01
PublicationDateYYYYMMDD 2019-07-01
PublicationDate_xml – month: 07
  year: 2019
  text: 2019-07-01
  day: 01
PublicationDecade 2010
PublicationTitle Cancer research (Chicago, Ill.)
PublicationYear 2019
SSID ssj0005105
Score 4.6930614
Snippet Targeted cancer therapy is based on exploiting selective dependencies of tumor cells. By leveraging recent large-scale genomic profiling and functional...
SourceID crossref
SourceType Aggregation Database
StartPage 2560
Title Abstract 2560: Werner syndrome helicase is a selective vulnerability of microsatellite instability-high tumor cells
Volume 79
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1LS8NAEF6qgngRn_hmD97CRmi6TeKtiiJqFVFpb2HzooX4IEk9-J_9D87sI4laxHpZ0pRMtp2P3dmZb2YIORRO5Mex6zKM2rFOO_KY8N2UCY-n3BNdL1Zsi5vuxWPncsiHrdZHg7U0KUM7ep-aV_IfrcI90Ctmyc6g2Uoo3IBr0C-MoGEY_6TjXoiOiqi00KLAs_0gwb71VRkCMAPRJ1ck2LZcWIXseYNUobdJhtWmJTFWhdiRl1cIWZ6zxDoiYDSqbxkWNLbKydNLbqGXv2ias6eImdzSFYNGMiSsuB1y7ckyu-FpuB4nMvhzD_BoBPMzMRLstpBbhDKm78fZ27jaLq4EWPa5pqAVhoKmjgHIFRxhrP-kmyY5G6jLLK2ZIiLX_cGNa0NmUxnXhlmuPcY7qrePndQrtNtRNSjNEq760RioOoHsiFpTh_TazFXnAr3Pm48_9xCOeRHVe-xeX86tfrxZs_vbXloxHOXZinsBiglQTKDEBChmjixg3UZs9XB1Vxe355pxa361TjgDMUdTZ9MwpRo20cMKWdaHGdpTyFwlreR5jSz2NV1jnRQGoBQFHVMFT2rgSQ086bigglbwpF_gSV9S-hWe9Ds8qYQnlfDcIPz87OH0gplJB6-qoErw65_lbJL5Z4DlFqG-74E16YdOhMyEuB2mruPErhOKNoxxuE3s2WTvzPrALlmqgbpH5st8kuyDVVqGB1KXn7jAi2c
link.rule.ids 314,780,784,27924,27925
linkProvider Colorado Alliance of Research Libraries
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=Abstract+2560%3A+Werner+syndrome+helicase+is+a+selective+vulnerability+of+microsatellite+instability-high+tumor+cells&rft.jtitle=Cancer+research+%28Chicago%2C+Ill.%29&rft.au=Lieb%2C+Simone&rft.au=Blaha-Ostermann%2C+Silvia&rft.au=Kamper%2C+Elisabeth&rft.au=Ehrenh%C3%B6fer-W%C3%B6lfer%2C+Katharina&rft.date=2019-07-01&rft.issn=0008-5472&rft.eissn=1538-7445&rft.volume=79&rft.issue=13_Supplement&rft.spage=2560&rft.epage=2560&rft_id=info:doi/10.1158%2F1538-7445.AM2019-2560&rft.externalDBID=n%2Fa&rft.externalDocID=10_1158_1538_7445_AM2019_2560
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0008-5472&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0008-5472&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0008-5472&client=summon