TY - JOUR
T1 - Subtype-specific transcriptional regulators in breast tumors subjected to genetic and epigenetic alterations
AU - Zhu, Qian
AU - Tekpli, Xavier
AU - Troyanskaya, Olga G.
AU - Kristensen, Vessela N.
N1 - Funding Information:
The work was supported in part by the National Institute of Health (NIH) award R01 HG005998 and partially supported by the National Science Foundation (NSF) CAREER award (DBI-0546275), NIH awards R01 GM071966 and R24OD011194 to O.G.T. O.G.T. is a Senior Fellow of the Canadian Institute For Advanced Research in the Genetic Networks group. X.T has been a fellow of the Norwegian Cancer Society. V.N.K. has been supported by Radiumhospitalets Legater.
Publisher Copyright:
© 2020 Oxford University Press. All rights reserved.
PY - 2020/2/15
Y1 - 2020/2/15
N2 - Motivation: Breast cancer consists of multiple distinct tumor subtypes, and results from epigenetic and genetic aberrations that give rise to distinct transcriptional profiles. Despite previous efforts to understand transcriptional deregulation through transcription factor networks, the transcriptional mechanisms leading to subtypes of the disease remain poorly understood. Results: We used a sophisticated computational search of thousands of expression datasets to define extended signatures of distinct breast cancer subtypes. Using ENCODE ChIP-seq data of surrogate cell lines and motif analysis we observed that these subtypes are determined by a distinct repertoire of lineage-specific transcription factors. Furthermore, specific pattern and abundance of copy number and DNA methylation changes at these TFs and targets, compared to other genes and to normal cells were observed. Overall, distinct transcriptional profiles are linked to genetic and epigenetic alterations at lineage-specific transcriptional regulators in breast cancer subtypes.
AB - Motivation: Breast cancer consists of multiple distinct tumor subtypes, and results from epigenetic and genetic aberrations that give rise to distinct transcriptional profiles. Despite previous efforts to understand transcriptional deregulation through transcription factor networks, the transcriptional mechanisms leading to subtypes of the disease remain poorly understood. Results: We used a sophisticated computational search of thousands of expression datasets to define extended signatures of distinct breast cancer subtypes. Using ENCODE ChIP-seq data of surrogate cell lines and motif analysis we observed that these subtypes are determined by a distinct repertoire of lineage-specific transcription factors. Furthermore, specific pattern and abundance of copy number and DNA methylation changes at these TFs and targets, compared to other genes and to normal cells were observed. Overall, distinct transcriptional profiles are linked to genetic and epigenetic alterations at lineage-specific transcriptional regulators in breast cancer subtypes.
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U2 - 10.1093/bioinformatics/btz709
DO - 10.1093/bioinformatics/btz709
M3 - Article
C2 - 31529022
AN - SCOPUS:85080842930
SN - 1367-4803
VL - 36
SP - 994
EP - 999
JO - Bioinformatics
JF - Bioinformatics
IS - 4
ER -