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 Kagan & 13 others David 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

    Cite this

    Petrovics, G., Li, H., Stümpel, T., Tan, S-H., Young, D., Katta, S., ... Srivastava, S. (2015). A novel genomic alteration of LSAMP associates with aggressive prostate cancer in African American men. EBioMedicine, 2(12), 1957-1964. https://doi.org/10.1016/j.ebiom.2015.10.028
    Petrovics, Gyorgy ; Li, Hua ; Stümpel, Tanja ; Tan, Shyh-Han ; Young, Denise ; Katta, Shilpa ; Li, Qiyuan ; Ying, Kai ; Klocke, Bernward ; Ravindranath, Lakshmi ; Kohaar, Indu ; Chen, Yongmei ; Ribli, Dezső ; Grote, Korbinian ; Zou, Hua ; Cheng, Joseph ; Dalgard, Clifton L. ; Zhang, Shimin ; Csabai, Istvan ; Kagan, Jacob ; Takeda, David ; Loda, Massimo ; Scherf, Matthias ; Seifert, Martin ; Gaiser, Timo ; McLeod, David G. ; Szallasi, Zoltan Imre ; Ebner, Reinhard ; Werner, Thomas ; Sesterhenn, Isabell A ; Freedman, Matthew ; Dobi, Albert ; Srivastava, Shiv. / A novel genomic alteration of LSAMP associates with aggressive prostate cancer in African American men. In: EBioMedicine. 2015 ; Vol. 2, No. 12. pp. 1957-1964.
    @article{3c9ab847fe1e4d5a8e18731ef4709fc0,
    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.",
    keywords = "African American, ERG, Genome, LSAMP, PTEN, Prostate cancer",
    author = "Gyorgy Petrovics and Hua Li and Tanja St{\"u}mpel and Shyh-Han Tan and Denise Young and Shilpa Katta and Qiyuan Li and Kai Ying and Bernward Klocke and Lakshmi Ravindranath and Indu Kohaar and Yongmei Chen and Dezső Ribli and Korbinian Grote and Hua Zou and Joseph Cheng and Dalgard, {Clifton L.} and Shimin Zhang and Istvan Csabai and Jacob Kagan and David Takeda and Massimo Loda and Matthias Scherf and Martin Seifert and Timo Gaiser and McLeod, {David G.} and Szallasi, {Zoltan Imre} and Reinhard Ebner and Thomas Werner and Sesterhenn, {Isabell A} and Matthew Freedman and Albert Dobi and Shiv Srivastava",
    note = "{\circledC} 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/).",
    year = "2015",
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    Petrovics, G, Li, H, Stümpel, T, Tan, S-H, Young, D, Katta, S, Li, Q, Ying, K, Klocke, B, Ravindranath, L, Kohaar, I, Chen, Y, Ribli, D, Grote, K, Zou, H, Cheng, J, Dalgard, CL, Zhang, S, Csabai, I, Kagan, J, Takeda, D, Loda, M, Scherf, M, Seifert, M, Gaiser, T, McLeod, DG, Szallasi, ZI, Ebner, R, Werner, T, Sesterhenn, IA, Freedman, M, Dobi, A & Srivastava, S 2015, 'A novel genomic alteration of LSAMP associates with aggressive prostate cancer in African American men', EBioMedicine, vol. 2, no. 12, pp. 1957-1964. https://doi.org/10.1016/j.ebiom.2015.10.028

    A novel genomic alteration of LSAMP associates with aggressive prostate cancer in African American men. / Petrovics, Gyorgy; Li, Hua; Stümpel, Tanja; Tan, Shyh-Han; Young, Denise; Katta, Shilpa; Li, Qiyuan; Ying, Kai; Klocke, Bernward; Ravindranath, Lakshmi; Kohaar, Indu; Chen, Yongmei; Ribli, Dezső; Grote, Korbinian; Zou, Hua; Cheng, Joseph; Dalgard, Clifton L.; Zhang, Shimin; Csabai, Istvan; Kagan, Jacob; Takeda, David; Loda, Massimo; Scherf, Matthias; Seifert, Martin; Gaiser, Timo; McLeod, David G.; Szallasi, Zoltan Imre; Ebner, Reinhard; Werner, Thomas; Sesterhenn, Isabell A; Freedman, Matthew; Dobi, Albert; Srivastava, Shiv.

    In: EBioMedicine, Vol. 2, No. 12, 2015, p. 1957-1964.

    Research output: Contribution to journalJournal articleResearchpeer-review

    TY - JOUR

    T1 - A novel genomic alteration of LSAMP associates with aggressive prostate cancer in African American men

    AU - Petrovics, Gyorgy

    AU - Li, Hua

    AU - Stümpel, Tanja

    AU - Tan, Shyh-Han

    AU - Young, Denise

    AU - Katta, Shilpa

    AU - Li, Qiyuan

    AU - Ying, Kai

    AU - Klocke, Bernward

    AU - Ravindranath, Lakshmi

    AU - Kohaar, Indu

    AU - Chen, Yongmei

    AU - Ribli, Dezső

    AU - Grote, Korbinian

    AU - Zou, Hua

    AU - Cheng, Joseph

    AU - Dalgard, Clifton L.

    AU - Zhang, Shimin

    AU - Csabai, Istvan

    AU - Kagan, Jacob

    AU - Takeda, David

    AU - Loda, Massimo

    AU - Scherf, Matthias

    AU - Seifert, Martin

    AU - Gaiser, Timo

    AU - McLeod, David G.

    AU - Szallasi, Zoltan Imre

    AU - Ebner, Reinhard

    AU - Werner, Thomas

    AU - Sesterhenn, Isabell A

    AU - Freedman, Matthew

    AU - Dobi, Albert

    AU - Srivastava, Shiv

    N1 - © 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/).

    PY - 2015

    Y1 - 2015

    N2 - 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.

    AB - 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.

    KW - African American

    KW - ERG

    KW - Genome

    KW - LSAMP

    KW - PTEN

    KW - Prostate cancer

    U2 - 10.1016/j.ebiom.2015.10.028

    DO - 10.1016/j.ebiom.2015.10.028

    M3 - Journal article

    VL - 2

    SP - 1957

    EP - 1964

    JO - EBioMedicine

    JF - EBioMedicine

    SN - 2352-3964

    IS - 12

    ER -