Cistrome Partitioning Reveals Convergence of Somatic Mutations and Risk Variants on Master Transcription Regulators in Primary Prostate Tumors.
Cancer Cell
; 36(6): 674-689.e6, 2019 12 09.
Article
em En
| MEDLINE
| ID: mdl-31735626
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Regulação Neoplásica da Expressão Gênica
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Proteínas de Homeodomínio
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Fator 3-alfa Nuclear de Hepatócito
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Humans
/
Male
Idioma:
En
Revista:
Cancer Cell
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Canadá