Epigenomic and Transcriptomic Characterization of Secondary Breast Cancers
Background Molecular alterations impact tumor prognosis and response to treatment. This study was designed to identify transcriptomic and epigenomic signatures of breast cancer (BC) tumors from patients with any prior malignancy. Methods RNA-sequencing and genome-wide DNA methylation profiles from B...
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Published in | Annals of surgical oncology Vol. 25; no. 10; pp. 3082 - 3087 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Cham
Springer International Publishing
01.10.2018
Springer Nature B.V |
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Abstract | Background
Molecular alterations impact tumor prognosis and response to treatment. This study was designed to identify transcriptomic and epigenomic signatures of breast cancer (BC) tumors from patients with any prior malignancy.
Methods
RNA-sequencing and genome-wide DNA methylation profiles from BCs were generated in the Cancer Genome Atlas project. Patients with secondary breast cancer (SBC) were separated by histological subtype and matched to primary breast cancer controls to create two independent cohorts of invasive ductal (IDC,
n
= 36) and invasive lobular (ILC,
n
= 40) carcinoma. Differentially expressed genes, as well as differentially methylated genomic regions, were integrated to identify epigenetically regulated abnormal gene pathways in SBCs.
Results
Differentially expressed genes were identified in IDC SBCs (
n
= 727) and in ILC SBCs (
n
= 261; Wilcoxon’s test;
P
< 0.05). In IDC SBCs, 105 genes were upregulated and hypomethylated, including an estrogen receptor gene, and 73 genes were downregulated and hypermethylated, including genes involved in antigen presentation and interferon response pathways (
HLA
-
E
,
IRF8
, and
RELA
). In ILC SBCs, however, only 17 genes were synchronously hypomethylated and upregulated, whereas 46 genes hypermethylated and downregulated. Interestingly, the SBC gene expression signatures closely corresponded with each histological subtype with only 1.51% of genes overlapping between the two histological subtypes.
Conclusions
Differential gene expression and DNA methylation signatures are seen in both IDC and ILC SBCs, including genes that are relevant to tumor growth and proliferation. Differences in gene expression signatures corresponding with each histological subtype emphasize the importance of disease subtype-specific evaluations of molecular alterations. |
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AbstractList | BackgroundMolecular alterations impact tumor prognosis and response to treatment. This study was designed to identify transcriptomic and epigenomic signatures of breast cancer (BC) tumors from patients with any prior malignancy.MethodsRNA-sequencing and genome-wide DNA methylation profiles from BCs were generated in the Cancer Genome Atlas project. Patients with secondary breast cancer (SBC) were separated by histological subtype and matched to primary breast cancer controls to create two independent cohorts of invasive ductal (IDC, n = 36) and invasive lobular (ILC, n = 40) carcinoma. Differentially expressed genes, as well as differentially methylated genomic regions, were integrated to identify epigenetically regulated abnormal gene pathways in SBCs.ResultsDifferentially expressed genes were identified in IDC SBCs (n = 727) and in ILC SBCs (n = 261; Wilcoxon’s test; P < 0.05). In IDC SBCs, 105 genes were upregulated and hypomethylated, including an estrogen receptor gene, and 73 genes were downregulated and hypermethylated, including genes involved in antigen presentation and interferon response pathways (HLA-E, IRF8, and RELA). In ILC SBCs, however, only 17 genes were synchronously hypomethylated and upregulated, whereas 46 genes hypermethylated and downregulated. Interestingly, the SBC gene expression signatures closely corresponded with each histological subtype with only 1.51% of genes overlapping between the two histological subtypes.ConclusionsDifferential gene expression and DNA methylation signatures are seen in both IDC and ILC SBCs, including genes that are relevant to tumor growth and proliferation. Differences in gene expression signatures corresponding with each histological subtype emphasize the importance of disease subtype-specific evaluations of molecular alterations. Background Molecular alterations impact tumor prognosis and response to treatment. This study was designed to identify transcriptomic and epigenomic signatures of breast cancer (BC) tumors from patients with any prior malignancy. Methods RNA-sequencing and genome-wide DNA methylation profiles from BCs were generated in the Cancer Genome Atlas project. Patients with secondary breast cancer (SBC) were separated by histological subtype and matched to primary breast cancer controls to create two independent cohorts of invasive ductal (IDC, n = 36) and invasive lobular (ILC, n = 40) carcinoma. Differentially expressed genes, as well as differentially methylated genomic regions, were integrated to identify epigenetically regulated abnormal gene pathways in SBCs. Results Differentially expressed genes were identified in IDC SBCs ( n = 727) and in ILC SBCs ( n = 261; Wilcoxon’s test; P < 0.05). In IDC SBCs, 105 genes were upregulated and hypomethylated, including an estrogen receptor gene, and 73 genes were downregulated and hypermethylated, including genes involved in antigen presentation and interferon response pathways ( HLA - E , IRF8 , and RELA ). In ILC SBCs, however, only 17 genes were synchronously hypomethylated and upregulated, whereas 46 genes hypermethylated and downregulated. Interestingly, the SBC gene expression signatures closely corresponded with each histological subtype with only 1.51% of genes overlapping between the two histological subtypes. Conclusions Differential gene expression and DNA methylation signatures are seen in both IDC and ILC SBCs, including genes that are relevant to tumor growth and proliferation. Differences in gene expression signatures corresponding with each histological subtype emphasize the importance of disease subtype-specific evaluations of molecular alterations. Molecular alterations impact tumor prognosis and response to treatment. This study was designed to identify transcriptomic and epigenomic signatures of breast cancer (BC) tumors from patients with any prior malignancy. RNA-sequencing and genome-wide DNA methylation profiles from BCs were generated in the Cancer Genome Atlas project. Patients with secondary breast cancer (SBC) were separated by histological subtype and matched to primary breast cancer controls to create two independent cohorts of invasive ductal (IDC, n = 36) and invasive lobular (ILC, n = 40) carcinoma. Differentially expressed genes, as well as differentially methylated genomic regions, were integrated to identify epigenetically regulated abnormal gene pathways in SBCs. Differentially expressed genes were identified in IDC SBCs (n = 727) and in ILC SBCs (n = 261; Wilcoxon's test; P < 0.05). In IDC SBCs, 105 genes were upregulated and hypomethylated, including an estrogen receptor gene, and 73 genes were downregulated and hypermethylated, including genes involved in antigen presentation and interferon response pathways (HLA-E, IRF8, and RELA). In ILC SBCs, however, only 17 genes were synchronously hypomethylated and upregulated, whereas 46 genes hypermethylated and downregulated. Interestingly, the SBC gene expression signatures closely corresponded with each histological subtype with only 1.51% of genes overlapping between the two histological subtypes. Differential gene expression and DNA methylation signatures are seen in both IDC and ILC SBCs, including genes that are relevant to tumor growth and proliferation. Differences in gene expression signatures corresponding with each histological subtype emphasize the importance of disease subtype-specific evaluations of molecular alterations. |
Author | Marzese, Diego M. Salomon, Matthew P. Graff-Baker, Amanda N. Orozco, Javier I. J. Goldfarb, Melanie Hoon, Dave S. B. |
Author_xml | – sequence: 1 givenname: Amanda N. surname: Graff-Baker fullname: Graff-Baker, Amanda N. organization: Center for Endocrine Tumors and Disorders, John Wayne Cancer Institute at Providence Saint John’s Health Center – sequence: 2 givenname: Javier I. J. surname: Orozco fullname: Orozco, Javier I. J. organization: Center for Endocrine Tumors and Disorders, John Wayne Cancer Institute at Providence Saint John’s Health Center – sequence: 3 givenname: Diego M. surname: Marzese fullname: Marzese, Diego M. organization: Center for Endocrine Tumors and Disorders, John Wayne Cancer Institute at Providence Saint John’s Health Center – sequence: 4 givenname: Matthew P. surname: Salomon fullname: Salomon, Matthew P. organization: Center for Endocrine Tumors and Disorders, John Wayne Cancer Institute at Providence Saint John’s Health Center – sequence: 5 givenname: Dave S. B. surname: Hoon fullname: Hoon, Dave S. B. organization: Center for Endocrine Tumors and Disorders, John Wayne Cancer Institute at Providence Saint John’s Health Center – sequence: 6 givenname: Melanie surname: Goldfarb fullname: Goldfarb, Melanie email: melaniegoldfarbmd@gmail.com, goldfarbm@jwci.org organization: Center for Endocrine Tumors and Disorders, John Wayne Cancer Institute at Providence Saint John’s Health Center |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29956094$$D View this record in MEDLINE/PubMed |
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CitedBy_id | crossref_primary_10_1186_s13058_021_01418_7 crossref_primary_10_1016_j_bios_2019_111386 crossref_primary_10_1002_1878_0261_12978 crossref_primary_10_3892_wasj_2019_10 |
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Copyright | Society of Surgical Oncology 2018 Annals of Surgical Oncology is a copyright of Springer, (2018). All Rights Reserved. |
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Keywords | Interferon Response Pathway The Cancer Genome Atlas (TCGA) Duct Invasion (IDC) Secondary Breast Cancer (SBC) Epigenomic Signatures |
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Molecular alterations impact tumor prognosis and response to treatment. This study was designed to identify transcriptomic and epigenomic signatures... Molecular alterations impact tumor prognosis and response to treatment. This study was designed to identify transcriptomic and epigenomic signatures of breast... BackgroundMolecular alterations impact tumor prognosis and response to treatment. This study was designed to identify transcriptomic and epigenomic signatures... BACKGROUNDMolecular alterations impact tumor prognosis and response to treatment. This study was designed to identify transcriptomic and epigenomic signatures... |
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SubjectTerms | Aged Antigen presentation Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Breast cancer Breast Neoplasms - genetics Breast Neoplasms - pathology Breast Neoplasms - surgery Carcinoma, Ductal, Breast - genetics Carcinoma, Ductal, Breast - pathology Carcinoma, Ductal, Breast - surgery Carcinoma, Lobular - genetics Carcinoma, Lobular - pathology Carcinoma, Lobular - surgery DNA Methylation DNA sequencing Epigenomics Female Follow-Up Studies Gene expression Gene Expression Profiling Gene Expression Regulation, Neoplastic Genome, Human Genomes Histocompatibility antigen HLA Humans Invasiveness Malignancy Medicine Medicine & Public Health Middle Aged Neoplasms, Second Primary - genetics Neoplasms, Second Primary - pathology Neoplasms, Second Primary - surgery Oncology Patients Prognosis Receptor, ErbB-2 - metabolism Receptors, Estrogen - metabolism Receptors, Progesterone - metabolism RelA protein Ribonucleic acid RNA Surgery Surgical Oncology Transcriptome Translational Research and Biomarkers Tumors |
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Title | Epigenomic and Transcriptomic Characterization of Secondary Breast Cancers |
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