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CSN1 Somatic Mutations in Penile Squamous Cell Carcinoma

Feber, Andrew, Worth, Daniel C., Chakravarthy, Ankur, de Winter, Patricia, Shah, Kunal, Arya, Manit, Saqib, Muhammad, Nigam, Raj, Malone, Peter R., Tan, Wei Shen, and others. (2016) CSN1 Somatic Mutations in Penile Squamous Cell Carcinoma. Cancer Research, 76 (16). pp. 4720-4727. ISSN 0008-5472. (doi:10.1158/0008-5472.CAN-15-3134)

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http://dx.doi.org/10.1158/0008-5472.CAN-15-3134

Abstract

Other than an association with HPV infection, little is known about the genetic alterations determining the development of penile cancer. Although penile cancer is rare in the developed world, it presents a significant burden in developing countries. Here, we report the findings of whole-exome sequencing (WES) to determine the somatic mutational landscape of penile cancer. WES was performed on penile cancer and matched germline DNA from 27 patients undergoing surgical resection. Targeted resequencing of candidate genes was performed in an independent 70 patient cohort. Mutation data were also integrated with DNA methylation and copy-number information from the same patients. We identified an HPV-associated APOBEC mutation signature and an NpCpG signature in HPV-negative disease. We also identified recurrent mutations in the novel penile cancer tumor suppressor genes CSN1(GPS1) and FAT1. Expression of CSN1 mutants in cells resulted in colocalization with AGO2 in cytoplasmic P-bodies, ultimately leading to the loss of miRNA-mediated gene silencing, which may contribute to disease etiology. Our findings represent the first comprehensive analysis of somatic alterations in penile cancer, highlighting the complex landscape of alterations in this malignancy.

Item Type: Article
DOI/Identification number: 10.1158/0008-5472.CAN-15-3134
Additional information: Copyright © 2016 American Association for Cancer Research. Output published while author at another university and available from that institution’s repository, UCL Discovery, JAC 25/07/2018
Uncontrolled keywords: science & technology, life sciences & biomedicine, oncology, human cancers, tumor types, protein, COP9, phosphorylation, deamination, expression, domain, P53
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Tim Fenton
Date Deposited: 21 Apr 2017 13:40 UTC
Last Modified: 10 Jan 2020 12:57 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/61502 (The current URI for this page, for reference purposes)
Fenton, Tim: https://orcid.org/0000-0002-4737-8233
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