Subtype-specific transcriptional regulators in breast tumors subjected to genetic and epigenetic alterations.

TitleSubtype-specific transcriptional regulators in breast tumors subjected to genetic and epigenetic alterations.
Publication TypeJournal Article
Year of Publication2020
AuthorsZhu, Q, Tekpli, X, Troyanskaya, OG, Kristensen, VN
JournalBioinformatics
Volume36
Issue4
Pagination994-999
Date Published2020 02 15
ISSN1367-4811
KeywordsBreast Neoplasms, DNA Methylation, Epigenesis, Genetic, Epigenomics, Humans, Transcription Factors
Abstract

<p><b>MOTIVATION: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>AVAILABILITY AND IMPLEMENTATION: </b>The analysis code and data are deposited at https://bitbucket.org/qzhu/breast.cancer.tf/.</p><p><b>SUPPLEMENTARY INFORMATION: </b>Supplementary data are available at Bioinformatics online.</p>

DOI10.1093/bioinformatics/btz709
Alternate JournalBioinformatics
PubMed ID31529022
PubMed Central IDPMC7031777
Grant ListR01 GM071966 / GM / NIGMS NIH HHS / United States
R01 HG005998 / HG / NHGRI NIH HHS / United States
R24 OD011194 / OD / NIH HHS / United States