title: A novel genomic alteration of LSAMP associates with aggressive prostate cancer in African American men.
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.
authors: 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.
authors: Gyorgy
authors: G
authors: Petrovics
authors: 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.
authors: Hua
authors: H
authors: Li
authors: Genomatix Software GmbH, MünchenE D-80335, Germany.
authors: Tanja
authors: T
authors: Stümpel
authors: 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.
authors: Shyh-Han
authors: SH
authors: Tan
authors: 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.
authors: Denise
authors: D
authors: Young
authors: 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.
authors: Shilpa
authors: S
authors: Katta
authors: Medical College, Xiamen University, Xiamen 361102, China; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
authors: Qiyuan
authors: Q
authors: Li
authors: 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.
authors: Kai
authors: K
authors: Ying
authors: Genomatix Software GmbH, MünchenE D-80335, Germany.
authors: Bernward
authors: B
authors: Klocke
authors: 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.
authors: Lakshmi
authors: L
authors: Ravindranath
authors: 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.
authors: Indu
authors: I
authors: Kohaar
authors: 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.
authors: Yongmei
authors: Y
authors: Chen
authors: 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.
authors: Dezső
authors: D
authors: Ribli
authors: Genomatix Software GmbH, MünchenE D-80335, Germany.
authors: Korbinian
authors: K
authors: Grote
authors: CytoTest Inc., Rockville, MD 20850, USA.
authors: Hua
authors: H
authors: Zou
authors: CytoTest Inc., Rockville, MD 20850, USA.
authors: Joseph
authors: J
authors: Cheng
authors: Department of Anatomy, Physiology and Genetics, Collaborative Health Initiative Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors: Clifton L
authors: CL
authors: Dalgard
authors: Genitourinary Pathology, Joint Pathology Center, Silver Spring, MD 20910, USA.
authors: Shimin
authors: S
authors: Zhang
authors: 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.
authors: István
authors: I
authors: Csabai
authors: Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892, USA.
authors: Jacob
authors: J
authors: Kagan
authors: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; The Eli and Edythe L. Broad Institute, Cambridge, MA, USA.
authors: David
authors: D
authors: Takeda
authors: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; The Eli and Edythe L. Broad Institute, Cambridge, MA, USA.
authors: Massimo
authors: M
authors: Loda
authors: Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892, USA.
authors: Sudhir
authors: S
authors: Srivastava
authors: Genomatix Software GmbH, MünchenE D-80335, Germany.
authors: Matthias
authors: M
authors: Scherf
authors: Genomatix Software GmbH, MünchenE D-80335, Germany.
authors: Martin
authors: M
authors: Seifert
authors: Pathologisches Institut, Universitätsmedizin Mannheim, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim D-68167, Germany.
authors: Timo
authors: T
authors: Gaiser
authors: 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.
authors: David G
authors: DG
authors: McLeod
authors: 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.
authors: Zoltan
authors: Z
authors: Szallasi
authors: CytoTest Inc., Rockville, MD 20850, USA.
authors: Reinhard
authors: R
authors: Ebner
authors: 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.
authors: Thomas
authors: T
authors: Werner
authors: Genitourinary Pathology, Joint Pathology Center, Silver Spring, MD 20910, USA.
authors: Isabell A
authors: IA
authors: Sesterhenn
authors: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; The Eli and Edythe L. Broad Institute, Cambridge, MA, USA.
authors: Matthew
authors: M
authors: Freedman
authors: 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.
authors: Albert
authors: A
authors: Dobi
authors: 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.
authors: Shiv
authors: S
authors: Srivastava
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000368:Aged; D014408:Biomarkers, Tumor; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D016000:Cluster Analysis; D018450:Disease Progression; D058851:GPI-Linked Proteins / Q000235:genetics; D017353:Gene Deletion; D015321:Gene Rearrangement; D056726:Genetic Association Studies; D056426:Genetic Loci; D014644:Genetic Variation; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D051059:PTEN Phosphohydrolase; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor; D015816:Cell Adhesion Molecules, Neuronal; D058851:GPI-Linked Proteins; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; C095362:limbic system-associated membrane protein; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: African American; ERG; Genome; LSAMP; PTEN; Prostate cancer