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, Dezso Ribli, Korbinian Grote, Hua Zou, Joseph Cheng, Clifton L. Dalgard, Shimin Zhang, István Csabai, Jacob KaganDavid Takeda, Massimo Loda, Sudhir Srivastava, Matthias Scherf, Martin Seifert, Timo Gaiser, David G. McLeod, Zoltan Szallasi, Reinhard Ebner, Thomas Werner, Isabell A. Sesterhenn, Matthew Freedman*, Albert Dobi, Shiv Srivastava

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

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
Pages (from-to)1957-1964
Number of pages8
JournaleBioMedicine
Volume2
Issue number12
DOIs
StatePublished - 1 Dec 2015
Externally publishedYes

Keywords

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

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