Romanel, Alessandro; Garritano, Sonia; Stringa, Blerta; Blattner, Mirjam; Dalfovo, Davide; Chakravarty, Dimple; Soong, David; Cotter, Kellie Anne; Petris, Gianluca; Dhingra, Priyanka; Gasperini, Paola; Cereseto, Anna; Elemento, Olivier; Sboner, Andrea; Khurana, Ekta; Inga, Alberto; Rubin, Mark Andrew; Demichelis, Francesca (2017). Inherited determinants of early recurrent somatic mutations in prostate cancer. Nature communications, 8(1), p. 48. Nature Publishing Group 10.1038/s41467-017-00046-0
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Prostate cancer is a highly heritable molecularly and clinically heterogeneous disease. To discover germline events involved in prostate cancer predisposition, we develop a computational approach to nominate heritable facilitators of somatic genomic events in the context of the androgen receptor signaling. Here, we use a ranking score and benign prostate transcriptomes to identify a non-coding polymorphic regulatory element at 7p14.3 that associates with DNA repair and hormone-regulated transcript levels and with an early recurrent prostate cancer-specific somatic mutation in the Speckle-Type POZ protein (SPOP) gene. The locus shows allele-specific activity that is concomitantly modulated by androgen receptor and by CCAAT/enhancer-binding protein (C/EBP) beta (CEBPB). Deletion of this locus via CRISPR-Cas9 leads to deregulation of the genes predicted to interact with the 7p14.3 locus by Hi-C chromosome conformation capture data. This study suggests that a polymorphism at 7p14.3 may predispose to SPOP mutant prostate cancer subclass through a hormone-dependent DNA damage response.Prostate cancer is a heterogeneous disease, and many cases show somatic mutations of SPOP. Here, the authors show that a non-coding polymorphic regulatory element at 7p14.3 may predispose to SPOP mutant prostate cancer subclass through a hormone dependent DNA damage response.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie |
UniBE Contributor: |
Cotter, Kellie Anne, Rubin, Mark Andrew |
Subjects: |
500 Science 500 Science > 570 Life sciences; biology |
ISSN: |
2041-1723 |
Publisher: |
Nature Publishing Group |
Language: |
English |
Submitter: |
Marla Rittiner |
Date Deposited: |
02 Feb 2018 12:47 |
Last Modified: |
05 Dec 2022 15:10 |
Publisher DOI: |
10.1038/s41467-017-00046-0 |
PubMed ID: |
28663546 |
BORIS DOI: |
10.7892/boris.110780 |
URI: |
https://boris.unibe.ch/id/eprint/110780 |
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