Distinct Genomic Aberrations Associated with ERG Rearranged Prostate Cancer

被引:80
作者
Demichelis, Francesca [1 ,2 ]
Setlur, Sunita R. [3 ]
Beroukhim, Rameen [4 ,5 ,6 ,7 ,8 ]
Perner, Sven [1 ]
Korbel, Jan O. [9 ]
LaFargue, Christopher J. [1 ]
Pflueger, Dorothee [1 ,10 ]
Pina, Cara [3 ]
Hofer, Matthias D. [3 ]
Sboner, Andrea [9 ]
Svensson, Maria A. [1 ]
Rickman, David S. [1 ]
Urban, Alex [11 ]
Snyder, Michael [11 ]
Meyerson, Matthew [4 ,5 ,6 ,7 ,8 ]
Lee, Charles [3 ]
Gerstein, Mark B. [9 ,12 ,13 ]
Kuefer, Rainer [10 ]
Rubin, Mark A. [1 ]
机构
[1] Weill Cornell Med Ctr, Dept Pathol & Lab Med, New York, NY 10065 USA
[2] Weill Cornell Med Ctr, Inst Computat Biomed, New York, NY 10065 USA
[3] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA
[4] MIT, Broad Inst, Cambridge, MA 02142 USA
[5] Harvard Univ, Cambridge, MA 02142 USA
[6] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA
[7] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA
[8] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA
[9] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA
[10] Univ Hosp Ulm, Dept Urol, D-89075 Ulm, Germany
[11] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA
[12] Yale Univ, Interdepartmental Program Computat Biol & Bioinfo, New Haven, CT 06520 USA
[13] Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA
关键词
TMPRSS2-ERG GENE FUSION; EWS CHIMERIC TRANSCRIPTS; CHROMOSOMAL-ABERRATIONS; EXPRESSION; MCM7; TRANSLOCATION; AMPLIFICATION; DELETIONS; ONCOGENE; MARKERS;
D O I
10.1002/gcc.20647
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Emerging molecular and clinical data suggest that ETS fusion prostate cancer represents a distinct molecular subclass, driven most commonly by a hormonally regulated promoter and characterized by an aggressive natural history. The study of the genomic landscape of prostate cancer in the light of ETS fusion events is required to understand the foundation of this molecularly and clinically distinct subtype. We performed genome-wide profiling of 49 primary prostate cancers and identified 20 recurrent chromosomal copy number aberrations, mainly occurring as genomic losses. Co-occurring events included losses at 19q13.32 and 1p22.1. We discovered three genomic events associated with ERG rearranged prostate cancer, affecting 6q, 7q, and 16q. 6q loss in nonrearranged prostate cancer is accompanied by gene expression deregulation in an independent dataset and by protein deregulation of MYO6. To analyze copy number alterations within the ETS genes, we performed a comprehensive analysis of all 27 ETS genes and of the 3 Mbp genomic area between ERG and TMPRSS2 (21q) with an unprecedented resolution (30 bp). We demonstrate that high-resolution tiling arrays can be used to pinpoint breakpoints leading to fusion events. This study provides further support to define a distinct molecular subtype of prostate cancer based on the presence of ETS gene rearrangements. (C) 2009 Wiley-Liss, lnc.
引用
收藏
页码:366 / 380
页数:15
相关论文
共 47 条
[1]   Molecular cytogenetic analysis of prostatic adenocarcinomas from screening studies -: Early cancers may contain aggressive genetic features [J].
Alers, JC ;
Krijtenburg, PJ ;
Vis, AN ;
Hoedemaeker, RF ;
Wildhagen, MF ;
Hop, WCJ ;
van der Kwast, TH ;
Schröder, FH ;
Tanke, HJ ;
van Dekken, H .
AMERICAN JOURNAL OF PATHOLOGY, 2001, 158 (02) :399-406
[2]   Genomic profiling of MicroRNA and messenger RNA reveals deregulated MicroRNA expression in prostate cancer [J].
Ambs, Stefan ;
Prueitt, Robyn L. ;
Yi, Ming ;
Hudson, Robert S. ;
Howe, Tiffany M. ;
Petrocca, Fabio ;
Wallace, Tiffany A. ;
Liu, Chang-Gong ;
Volinia, Stefano ;
Calin, George A. ;
Yfantis, Harris G. ;
Stephens, Robert M. ;
Croce, Carlo M. .
CANCER RESEARCH, 2008, 68 (15) :6162-6170
[3]  
AMIN MB, 2003, GLEASON GRADING PROS, P116
[4]   Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal human prostate cancer [J].
Attard, G. ;
Clark, J. ;
Ambroisine, L. ;
Fisher, G. ;
Kovacs, G. ;
Flohr, P. ;
Berney, D. ;
Foster, C. S. ;
Fletcher, A. ;
Gerald, W. L. ;
Moller, H. ;
Reuter, V. ;
De Bono, J. S. ;
Scardino, P. ;
Cuzick, J. ;
Cooper, C. S. .
ONCOGENE, 2008, 27 (03) :253-263
[5]   Assessing the significance of chromosomal aberrations in cancer: Methodology and application to glioma [J].
Beroukhim, Rameen ;
Getz, Gad ;
Nghiemphu, Leia ;
Barretina, Jordi ;
Hsueh, Teli ;
Linhart, David ;
Vivanco, Igor ;
Lee, Jeffrey C. ;
Huang, Julie H. ;
Alexander, Sethu ;
Du, Jinyan ;
Kau, Tweeny ;
Thomas, Roman K. ;
Shah, Kinial ;
Soto, Horacio ;
Perner, Sven ;
Prensner, John ;
Debiasi, Ralph M. ;
Demichelis, Francesca ;
Hatton, Charlie ;
Rubin, Mark A. ;
Garraway, Levi A. ;
Nelson, Stan F. ;
Liau, Linda ;
Mischel, Paul S. ;
Cloughesy, Tim F. ;
Meyerson, Matthew ;
Golub, Todd A. ;
Lander, Eric S. ;
Mellinghoff, Ingo K. ;
Sellers, William R. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (50) :20007-20012
[6]   Sorting nexin-14, a gene expressed in motoneurons trapped by an in vitro preselection method [J].
Carroll, P ;
Renoncourt, Y ;
Gayet, O ;
De Bovis, B ;
Alonso, S .
DEVELOPMENTAL DYNAMICS, 2001, 221 (04) :431-442
[7]   Frequent dysregulation of the c-maf proto-oncogene at 16q23 by translocation to an Ig locus in multiple myeloma [J].
Chesi, M ;
Bergsagel, PL ;
Shonukan, OO ;
Martelli, ML ;
Brents, LA ;
Chen, T ;
Schröck, E ;
Ried, T ;
Kuehl, VM .
BLOOD, 1998, 91 (12) :4457-4463
[8]   EWS-FL11 fusion transcript structure is an independent determinant of prognosis in Ewing's sarcoma [J].
de Alava, E ;
Kawai, A ;
Healey, JH ;
Fligman, I ;
Meyers, PA ;
Huvos, AG ;
Gerald, WL ;
Jhanwar, SC ;
Argani, P ;
Antonescu, CR ;
Pardo-Mindan, FJ ;
Ginsberg, J ;
Womer, R ;
Lawlor, ER ;
Wunder, J ;
Andrulis, I ;
Sorensen, PHB ;
Barr, FG ;
Ladanyi, M .
JOURNAL OF CLINICAL ONCOLOGY, 1998, 16 (04) :1248-1255
[9]   GENE FUSION WITH AN ETS DNA-BINDING DOMAIN CAUSED BY CHROMOSOME-TRANSLOCATION IN HUMAN TUMORS [J].
DELATTRE, O ;
ZUCMAN, J ;
PLOUGASTEL, B ;
DESMAZE, C ;
MELOT, T ;
PETER, M ;
KOVAR, H ;
JOUBERT, I ;
DEJONG, P ;
ROULEAU, G ;
AURIAS, A ;
THOMAS, G .
NATURE, 1992, 359 (6391) :162-165
[10]   TMPRSS2: ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort [J].
Demichelis, F. ;
Fall, K. ;
Perner, S. ;
Andren, O. ;
Schmidt, F. ;
Setlur, S. R. ;
Hoshida, Y. ;
Mosquera, J-M ;
Pawitan, Y. ;
Lee, C. ;
Adami, H-O ;
Mucci, L. A. ;
Kantoff, P. W. ;
Andersson, S-O ;
Chinnaiyan, A. M. ;
Johansson, J-E ;
Rubin, M. A. .
ONCOGENE, 2007, 26 (31) :4596-4599