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Bioinformatics. 2019 Sep 16. pii: btz709. doi: 10.1093/bioinformatics/btz709. [Epub ahead of print]

Subtype-Specific Transcriptional Regulators in Breast Tumors Subjected to Genetic and Epigenetic Alterations.

Author information

1
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, 360 Longwood Ave, Boston, MA.
2
Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, Oslo, Norway.
3
Department of Clinical Molecular Biology (EpiGen), Division of Medicine, Akershus University Hospital, Lørenskog, Norway.
4
Department of Computer Science, Princeton University, Princeton, NJ, USA.
5
Lewis-Siegler Institute of Integrative Genomics, Princeton University, Princeton, NJ, USA.
6
Flatiron Institute, Simons Foundation, New York, NY, USA.
7
Institute for Clinical Medicine, University of Oslo, Oslo, Norway.

Abstract

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.

SUPPLEMENTARY INFORMATION:

Supplementary data are available at Bioinformatics online.

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