EBioMedicine (Dec 2015)
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,
- István Csabai,
- Jacob Kagan,
- David 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
Affiliations
- Gyorgy Petrovics
- Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD 20814, USA
- Hua Li
- Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD 20814, USA
- Tanja Stümpel
- Genomatix Software GmbH, MünchenE D-80335, Germany
- Shyh-Han Tan
- Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD 20814, USA
- Denise Young
- Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD 20814, USA
- Shilpa Katta
- Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD 20814, USA
- Qiyuan Li
- Medical College, Xiamen University, Xiamen 361102, China
- Kai Ying
- Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD 20814, USA
- Bernward Klocke
- Genomatix Software GmbH, MünchenE D-80335, Germany
- Lakshmi Ravindranath
- Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD 20814, USA
- Indu Kohaar
- Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD 20814, USA
- Yongmei Chen
- Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD 20814, USA
- Dezső Ribli
- Department of Physics of Complex Systems, Eötvös Loránd University, Budapest H-1117, Hungary
- Korbinian Grote
- Genomatix Software GmbH, MünchenE D-80335, Germany
- Hua Zou
- CytoTest Inc., Rockville, MD 20850, USA
- Joseph Cheng
- CytoTest Inc., Rockville, MD 20850, USA
- Clifton L. Dalgard
- Department of Anatomy, Physiology and Genetics, Collaborative Health Initiative Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
- Shimin Zhang
- Genitourinary Pathology, Joint Pathology Center, Silver Spring, MD 20910, USA
- István Csabai
- Department of Physics of Complex Systems, Eötvös Loránd University, Budapest H-1117, Hungary
- Jacob Kagan
- Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892, USA
- David Takeda
- Dana–Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Massimo Loda
- Dana–Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Sudhir Srivastava
- Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892, USA
- Matthias Scherf
- Genomatix Software GmbH, MünchenE D-80335, Germany
- Martin Seifert
- Genomatix Software GmbH, MünchenE D-80335, Germany
- Timo Gaiser
- Pathologisches Institut, Universitätsmedizin Mannheim, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim D-68167, Germany
- David G. McLeod
- Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD 20814, USA
- Zoltan Szallasi
- Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, DK -2800, Denmark
- Reinhard Ebner
- CytoTest Inc., Rockville, MD 20850, USA
- Thomas Werner
- Genomatix Software GmbH, MünchenE D-80335, Germany
- Isabell A. Sesterhenn
- Genitourinary Pathology, Joint Pathology Center, Silver Spring, MD 20910, USA
- Matthew Freedman
- Dana–Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- Albert Dobi
- Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD 20814, USA
- Shiv Srivastava
- Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD 20814, USA
- DOI
- https://doi.org/10.1016/j.ebiom.2015.10.028
- Journal volume & issue
-
Vol. 2,
no. 12
pp. 1957 – 1964
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.
Keywords
