A novel genomic alteration of LSAMP associates with aggressive prostate cancer in African American men

Gyorgy Petrovics, Hua Li, Tanja Stümpel, Shyh-Han Tan, Denise Young, Shilpa Katta, Qiyuan Li, Kai Ying, Bernward Klocke, Lakshmi Ravindranath, Indu Kohaar, Yongmei Chen, Dezső Ribli, Korbinian Grote, Hua Zou, Joseph Cheng, Clifton L. Dalgard, Shimin Zhang, Istvan Csabai, Jacob KaganDavid Takeda, Massimo Loda, Matthias Scherf, Martin Seifert, Timo Gaiser, David G. McLeod, Zoltan Imre Szallasi, Reinhard Ebner, Thomas Werner, Isabell A Sesterhenn, Matthew Freedman, Albert Dobi, Shiv Srivastava

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    Abstract

    Evaluation of cancer genomes in global context is of great interest in light of changing ethnic distribution of the world population. We focused our study on men of African ancestry because of their disproportionately higher rate of prostate cancer (CaP) incidence and mortality. We present a systematic whole genome analyses, revealing alterations that differentiate African American (AA) and Caucasian American (CA) CaP genomes. We discovered a recurrent deletion on chromosome 3q13.31 centering on the LSAMP locus that was prevalent in tumors from AA men (cumulative analyses of 435 patients: whole genome sequence, 14; FISH evaluations, 101; and SNP array, 320 patients). Notably, carriers of this deletion experienced more rapid disease progression. In contrast, PTEN and ERG common driver alterations in CaP were significantly lower in AA prostate tumors compared to prostate tumors from CA. Moreover, the frequency of inter-chromosomal rearrangements was significantly higher in AA than CA tumors. These findings reveal differentially distributed somatic mutations in CaP across ancestral groups, which have implications for precision medicine strategies.
    Original languageEnglish
    JournalEBioMedicine
    Volume2
    Issue number12
    Pages (from-to)1957-1964
    Number of pages8
    ISSN2352-3964
    DOIs
    Publication statusPublished - 2015

    Bibliographical note

    © 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

    Keywords

    • African American
    • ERG
    • Genome
    • LSAMP
    • PTEN
    • Prostate cancer

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