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

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.

EBioMedicine. 2015 Oct 31*** epublish ***

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

PubMed      Full Text Article

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. , 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. , Genomatix Software GmbH, MünchenE D-80335, Germany. , 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. , 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. , 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. , Medical College, Xiamen University, Xiamen 361102, China; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. , 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. , Genomatix Software GmbH, MünchenE D-80335, Germany. , 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. , 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. , 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. , Department of Physics of Complex Systems, Eötvös Loránd University, Budapest H-1117, Hungary; Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, DK -2800, Denmark. , Genomatix Software GmbH, MünchenE D-80335, Germany. , CytoTest Inc. , Rockville, MD 20850, USA. , CytoTest Inc. , Rockville, MD 20850, USA. , Department of Anatomy, Physiology and Genetics, Collaborative Health Initiative Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA. , Genitourinary Pathology, Joint Pathology Center, Silver Spring, MD 20910, USA. , Department of Physics of Complex Systems, Eötvös Loránd University, Budapest H-1117, Hungary; Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, DK -2800, Denmark. , Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892, USA. , Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; The Eli and Edythe L. Broad Institute, Cambridge, MA, USA. , Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; The Eli and Edythe L. Broad Institute, Cambridge, MA, USA. , Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892, USA. , Genomatix Software GmbH, MünchenE D-80335, Germany. , Genomatix Software GmbH, MünchenE D-80335, Germany. , Pathologisches Institut, Universitätsmedizin Mannheim, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim D-68167, Germany. , 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; Urology Service, Walter Reed National Military Medical Center, Bethesda, MD 20814, USA. , Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, DK -2800, Denmark; Children's Hospital Informatics Program at the Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 20115, USA; MTA-SE NAP, Brain Metastasis Research Group, Hungarian Academy of Sciences, 2nd Department of Pathology, Semmelweis University, Budapest H-1091, Hungary. , CytoTest Inc. , Rockville, MD 20850, USA. , Genomatix Software GmbH, MünchenE D-80335, Germany; Internal Medicine, Nephrology Division and Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA. , Genitourinary Pathology, Joint Pathology Center, Silver Spring, MD 20910, USA. , Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; The Eli and Edythe L. Broad Institute, Cambridge, MA, USA. , 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. , 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.

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