| Title: |
Inherited determinants of early recurrent somatic mutations in prostate cancer. |
| Authors: |
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 |
| Source: |
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 |
| Publisher Information: |
Nature Publishing Group |
| Publication Year: |
2017 |
| Collection: |
BORIS (Bern Open Repository and Information System, University of Bern) |
| Subject Terms: |
500 Science; 570 Life sciences; biology |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://boris.unibe.ch/110780/ |
| Availability: |
https://boris.unibe.ch/110780/1/41467_2017_Article_46.pdf; https://boris.unibe.ch/110780/ |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.1D202781 |
| Database: |
BASE |