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; 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

doi:10.1016/j.ebiom.2015.10.028

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 KaganDavid 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 language	English
Journal	EBioMedicine
Volume	2
Issue number	12
Pages (from-to)	1957-1964
Number of pages	8
ISSN	2352-3964
DOIs	https://doi.org/10.1016/j.ebiom.2015.10.028
Publication status	Published - 2015

Bibliographical note

Keywords

African American
ERG
Genome
LSAMP
PTEN
Prostate cancer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ebiom.2015.10.028

A novel genomic alteration of LSAMP associates with aggressive prostate cancer in African American menFinal published version, 1.07 MB

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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, C. L., Zhang, S., Csabai, I., ... 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 Dezs{\H o} 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 = "{\textcopyright} 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",

doi = "10.1016/j.ebiom.2015.10.028",

language = "English",

volume = "2",

pages = "1957--1964",

journal = "EBioMedicine",

issn = "2352-3964",

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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 journal › Journal article › Research › peer-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

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

C2 - 26844274

VL - 2

SP - 1957

EP - 1964

JO - EBioMedicine

JF - EBioMedicine

SN - 2352-3964

IS - 12

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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