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    CSN1 Somatic Mutations in Penile Squamous Cell Carcinoma 
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    CSN1 Somatic Mutations in Penile Squamous Cell Carcinoma

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    Published version
    Embargoed until: 5555-01-01
    Volume
    76
    Pagination
    4720 - 4727
    Publisher
    American Association for Cancer Research
    DOI
    10.1158/0008-5472.CAN-15-3134
    Journal
    CANCER RESEARCH
    Issue
    16
    ISSN
    0008-5472
    Metadata
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    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 miRNAmediated 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.
    Authors
    Feber, A; Worth, DC; Chakravarthy, A; de Winter, P; Shah, K; Arya, M; Saqib, M; Nigam, R; Malone, PR; Tan, WS
    URI
    https://qmro.qmul.ac.uk/xmlui/handle/123456789/56388
    Collections
    • Centre for Molecular Oncology [260]
    Copyright statements
    ©2016 American Association for Cancer Research.
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