Cistrome Partitioning Reveals Convergence of Somatic Mutations and Risk Variants on Master Transcription Regulators in Primary Prostate Tumors

Parisa Mazrooei, Ken J. Kron, Yanyun Zhu, Stanley Zhou, Giacomo Grillo, Tahmid Mehdi, Musaddeque Ahmed, Tesa M. Severson, Paul Guilhamon, Nicholas Sinnott Armstrong, Vincent Huang, Takafumi N. Yamaguchi, Michael Fraser, Theodorus van der Kwast, Paul C. Boutros, Housheng Hansen He, Andries M. Bergman, Robert G. Bristow, Wilbert Zwart (Corresponding author), Mathieu Lupien (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)

Abstract

Thousands of noncoding somatic single-nucleotide variants (SNVs) of unknown function are reported in tumors. Partitioning the genome according to cistromes reveals the enrichment of somatic SNVs in prostate tumors as opposed to adjacent normal tissue cistromes of master transcription regulators, including AR, FOXA1, and HOXB13. This parallels enrichment of prostate cancer genetic predispositions over these transcription regulators' tumor cistromes, exemplified at the 8q24 locus harboring both risk variants and somatic SNVs in cis-regulatory elements upregulating MYC expression. However, Massively Parallel Reporter Assays reveal that few SNVs can alter the transactivation potential of individual cis-regulatory elements. Instead, similar to inherited risk variants, SNVs accumulate in cistromes of master transcription regulators required for prostate cancer development.

Original languageEnglish
Pages (from-to)674-689.e6
Number of pages15
JournalCancer Cell
Volume36
Issue number6
DOIs
Publication statusPublished - 9 Dec 2019

Keywords

  • accessible chromatin
  • cis-regulatory elements
  • epigenetics
  • H3K27ac
  • noncoding mutations
  • prostate cancer
  • prostate tumor risk SNP
  • single-nucleotide variant
  • transcription factors
  • transcription regulators

Fingerprint Dive into the research topics of 'Cistrome Partitioning Reveals Convergence of Somatic Mutations and Risk Variants on Master Transcription Regulators in Primary Prostate Tumors'. Together they form a unique fingerprint.

Cite this