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

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