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

Publication date: Available online 14 November 2019Source: Cancer CellAuthor(s): 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, Mathieu LupienSummaryThousands 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.Graphical Abstract
Source: Cancer Cell - Category: Cancer & Oncology Source Type: research