Integrative Genomic Analyses Reveal an Androgen-Driven Somatic Alteration Landscape in Early-Onset Prostate Cancer

被引：258

作者：

Weischenfeldt, Joachim ^{[1
]}

Simon, Ronald ^{[2
]}

Feuerbach, Lars ^{[4
]}

Schlangen, Karin ^{[9
]}

Weichenhan, Dieter ^{[5
]}

Minner, Sarah ^{[2
]}

Wuttig, Daniela ^{[6
]}

Warnatz, Hans-Joerg ^{[9
]}

Stehr, Henning ^{[9
]}

Rausch, Tobias ^{[1
]}

Jaeger, Natalie ^{[4
]}

Gu, Lei ^{[5
]}

Bogatyrova, Olga ^{[5
]}

Stuetz, Adrian M. ^{[1
]}

Claus, Rainer ^{[5
]}

Eils, Juergen ^{[4
]}

Eils, Roland ^{[4
,13
,14
]}

Gerhaeuser, Clarissa ^{[5
]}

Huang, Po-Hsien ^{[5
]}

Hutter, Barbara ^{[4
]}

Kabbe, Rolf ^{[4
]}

Lawerenz, Christian ^{[4
]}

Radomski, Sylwester ^{[4
]}

Bartholomae, Cynthia C. ^{[7
,8
]}

Faelth, Maria ^{[6
]}

Gade, Stephan ^{[6
]}

Schmidt, Manfred ^{[7
,8
]}

Amschler, Nina ^{[2
]}

Hass, Thomas ^{[2
]}

Galal, Rami ^{[2
]}

Gjoni, Jovisa ^{[2
]}

Kuner, Ruprecht ^{[6
]}

Baer, Constance ^{[5
]}

Masser, Sawinee ^{[2
]}

von Kalle, Christof ^{[7
,8
]}

Zichner, Thomas ^{[1
]}

Benes, Vladimir ^{[15
]}

Raeder, Benjamin ^{[1
]}

Mader, Malte ^{[10
]}

Amstislavskiy, Vyacheslav ^{[9
]}

Avci, Meryem ^{[7
,8
]}

Lehrach, Hans ^{[9
]}

Parkhomchuk, Dmitri ^{[9
]}

Sultan, Marc ^{[9
]}

Burkhardt, Lia ^{[2
]}

Graefen, Markus ^{[3
]}

Huland, Hartwig ^{[3
]}

Kluth, Martina ^{[2
]}

Krohn, Antje ^{[2
]}

Sirma, Hueseyin ^{[2
]}

机构：

[1] European Mol Biol Lab, Genome Biol Unit, D-69117 Heidelberg, Germany

[2] Univ Med Ctr Hamburg Eppendorf, Inst Pathol, D-20246 Hamburg, Germany

[3] Univ Med Ctr Hamburg Eppendorf, Prostate Canc Ctr, Martini Clin, D-20246 Hamburg, Germany

[4] German Canc Res Ctr, Div Theoret Bioinformat, D-69120 Heidelberg, Germany

[5] German Canc Res Ctr, Div Epigen & Canc Risk Factors, D-69120 Heidelberg, Germany

[6] German Canc Res Ctr, Working Grp Canc Genome Res, D-69120 Heidelberg, Germany

[7] German Canc Res Ctr, Div Translat Oncol, D-69120 Heidelberg, Germany

[8] Natl Ctr Tumor Dis, D-69120 Heidelberg, Germany

[9] Max Planck Inst Mol Genet, Dept Vertebrate Genom, D-14195 Berlin, Germany

[10] Univ Hamburg, Ctr Bioinformat, D-20146 Hamburg, Germany

[11] European Bioinformat Inst, Cambridge CB10 1SD, England

[12] Univ Med Ctr Hamburg Eppendorf, Dept Urol, Sect Translat Prostate Canc Res, D-20246 Hamburg, Germany

[13] Heidelberg Univ, Inst Pharm & Mol Biotechnol, D-69120 Heidelberg, Germany

[14] Heidelberg Univ, Bioquant Ctr, D-69120 Heidelberg, Germany

[15] European Mol Biol Lab, Genom Core Facil, D-69117 Heidelberg, Germany

来源：

CANCER CELL | 2013年 / 23卷 / 02期

关键词：

GENE FUSIONS; PSA RECURRENCE; REARRANGEMENTS; RECEPTOR; MECHANISM; DELETION; MEN; TESTOSTERONE; PROGRESSION; EXPRESSION;

D O I：

10.1016/j.ccr.2013.01.002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Early-onset prostate cancer (EO-PCA) represents the earliest clinical manifestation of prostate cancer. To compare the genomic alteration landscapes of EO-PCA with "classical" (elderly-onset) PCA, we performed deep sequencing-based genomics analyses in 11 tumors diagnosed at young age, and pursued comparative assessments with seven elderly-onset PCA genomes. Remarkable age-related differences in structural rearrangement (SR) formation became evident, suggesting distinct disease pathomechanisms. Whereas EO-PCAs harbored a prevalence of balanced SRs, with a specific abundance of androgen-regulated ETS gene fusions including TMPRSS2:ERG, elderly-onset PCAs displayed primarily non-androgen-associated SRs. Data from a validation cohort of > 10,000 patients showed age-dependent androgen receptor levels and a prevalence of SRs affecting androgen-regulated genes, further substantiating the activity of a characteristic "androgen-type" pathomechanism in EO-PCA.

引用

页码：159 / 170

页数：12

共 52 条

[21] Mechanisms of Prostate Cancer Initiation and Progression [J].

Knudsen, Beatrice S. ;

Vasioukhin, Valera .

ADVANCES IN CANCER RESEARCH, VOL 109, 2010, 109 :1-50

[22] MUTATION AND CANCER - STATISTICAL STUDY OF RETINOBLASTOMA [J].

KNUDSON, AG .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1971, 68 (04) :820-&

[23] Genomic Deletion of PTEN Is Associated with Tumor Progression and Early PSA Recurrence in ERG Fusion-Positive and Fusion-Negative Prostate Cancer [J].

Krohn, Antje ;

Diedler, Tobias ;

Burkhardt, Lia ;

Mayer, Pascale-Sophie ;

De Silva, Colin ;

Meyer-Kornblum, Marie ;

Koetschau, Darja ;

Tennstedt, Pierre ;

Huang, Joseph ;

Gerhaeuser, Clarissa ;

Mader, Malte ;

Kurtz, Stefan ;

Sirma, Huesyin ;

Saad, Fred ;

Steuber, Thomas ;

Graefen, Markus ;

Plass, Christoph ;

Sauter, Guido ;

Simon, Ronald ;

Minner, Sarah ;

Schlomm, Thorsten .

AMERICAN JOURNAL OF PATHOLOGY, 2012, 181 (02) :401-412

[24] Exome sequencing identifies a spectrum of mutation frequencies in advanced and lethal prostate cancers [J].

Kumar, Akash ;

White, Thomas A. ;

MacKenzie, Alexandra P. ;

Clegg, Nigel ;

Lee, Choli ;

Dumpit, Ruth F. ;

Coleman, Ilsa ;

Ng, Sarah B. ;

Salipante, Stephen J. ;

Rieder, Mark J. ;

Nickerson, Deborah A. ;

Corey, Eva ;

Lange, Paul H. ;

Morrissey, Colm ;

Vessella, Robert L. ;

Nelson, Peter S. ;

Shendure, Jay .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (41) :17087-17092

[25] Expression and degradation of androgen receptor: Mechanism and clinical implication [J].

Lee, DK ;

Chang, CS .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2003, 88 (09) :4043-4054

[26]

Ley TJ, 2008, NATURE, V456, P66, DOI 10.1038/nature07485

[27] Fast and accurate short read alignment with Burrows-Wheeler transform [J].

Li, Heng ;

Durbin, Richard .

BIOINFORMATICS, 2009, 25 (14) :1754-1760

[28] Long-term prediction of prostate cancer up to 25 years before diagnosis of prostate cancer using prostate kallikreins measured at age 44 to 50 years [J].

Lilja, Hans ;

Ulmert, David ;

Bjoerk, Thomas ;

Becker, Charlotte ;

Serio, Angel M. ;

Nilsson, Jan-Ake ;

Abrahamsson, Per-Anders ;

Vickers, Andrew J. ;

Berglund, Goran .

JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (04) :431-436

[29] Nuclear Receptor-Induced Chromosomal Proximity and DNA Breaks Underlie Specific Translocations in Cancer [J].

Lin, Chunru ;

Yang, Liuqing ;

Tanasa, Bogdan ;

Hutt, Kasey ;

Ju, Bong-gun ;

Ohgi, Kenny ;

Zhang, Jie ;

Rose, David W. ;

Fu, Xiang-Dong ;

Glass, Christopher K. ;

Rosenfeld, Michael G. .

CELL, 2009, 139 (06) :1069-1083

[30] Treatment and Survival Outcomes in Young Men Diagnosed With Prostate Cancer [J].

Lin, Daniel W. ;

Porter, Michael ;

Montgomery, Bruce .

CANCER, 2009, 115 (13) :2863-2871

← 1 2 3 4 5 6 →