Molecular Evolution of Early-Onset Prostate Cancer Identifies Molecular Risk Markers and Clinical Trajectories

被引：181

作者：

Gerhauser, Clarissa ^{[1
]}

Favero, Francesco ^{[2
,3
]}

Risch, Thomas ^{[4
]}

Simon, Ronald ^{[5
]}

Feuerbach, Lars ^{[6
]}

Assenov, Yassen ^{[1
]}

Heckmann, Doreen ^{[7
,8
]}

Sidiropoulos, Nikos ^{[2
,3
]}

Waszak, Sebastian M. ^{[9
]}

Huebschmann, Daniel ^{[10
,11
,12
]}

Urbanucci, Alfonso ^{[13
,14
,15
]}

Girma, Etsehiwot G. ^{[2
,3
]}

Kuryshev, Vladimir ^{[7
,8
]}

Klimczak, Leszek J. ^{[16
]}

Saini, Natalie ^{[17
]}

Stuetz, Adrian M. ^{[9
]}

Weichenhan, Dieter ^{[1
]}

Boettcher, Lisa-Marie ^{[5
]}

Toth, Reka ^{[1
]}

Hendriksen, Josephine D. ^{[2
,3
]}

Koop, Christina ^{[5
]}

Lutsik, Pavlo ^{[1
]}

Matzk, Soeren ^{[4
]}

Warnatz, Hans-Joerg ^{[4
]}

Amstislayskiy, Vyacheslav ^{[4
]}

Feuerstein, Clarissa ^{[1
,18
]}

Raeder, Benjamin ^{[9
]}

Bogatyrova, Olga ^{[1
]}

Schmitz, Eva-Maria ^{[19
]}

Hube-Magg, Claudia ^{[5
]}

Kluth, Martina ^{[5
]}

Huland, Hartwig ^{[20
]}

Graefen, Markus ^{[20
]}

Lawerenz, Chris ^{[10
]}

Henry, Gervaise H. ^{[21
]}

Yamaguchi, Takafumi N. ^{[22
]}

Malewska, Alicia ^{[21
]}

Meiners, Jan ^{[5
]}

Schilling, Daniela ^{[7
,23
,24
]}

Reisinger, Eva ^{[10
]}

Eils, Roland ^{[10
,11
]}

Schlesner, Matthias ^{[10
,25
]}

Strand, Douglas W. ^{[21
]}

Bristow, Robert G. ^{[26
]}

Boutros, Paul C. ^{[27
,28
]}

von Kalle, Christof ^{[8
,29
]}

Gordenin, Dmitry ^{[17
]}

Sueltmann, Holger ^{[7
,8
]}

Brors, Benedikt ^{[6
,8
,30
]}

Sauter, Guido ^{[5
]}

机构：

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

[2] Rigshosp, Finsen Lab, DK-2200 Copenhagen, Denmark

[3] Univ Copenhagen, Biotech Res & Innovat Ctr, DK-2200 Copenhagen, Denmark

[4] Max Planck Inst Mol Genet, Otto Warburg Lab Gene Regulat & Syst Biol Canc, Ihnestr 63-73, D-14195 Berlin, Germany

[5] Univ Med Ctr Hamburg Eppendorf, Dept Pathol, D-20246 Hamburg, Germany

[6] German Canc Res Ctr, Div Appl Bioinformat, Neuenheimer Feld 280, D-69120 Heidelberg, Germany

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

[8] German Canc Consortium DKTK, D-69120 Heidelberg, Germany

[9] European Mol Biol Lab, Genome Biol Unit, D-69120 Heidelberg, Germany

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

[11] Heidelberg Univ, Inst Pharm & Mol Biotechnol & Bioquant, Dept Bioinformat & Funct Genom, D-69120 Heidelberg, Germany

[12] Univ Hosp, Dept Pediat Immunol Hematol & Oncol, D-69120 Heidelberg, Germany

[13] Univ Oslo, Ctr Mol Med Norway, Nord European Mol Biol Lab Partnership, Forskningspk, N-0316 Oslo, Norway

[14] Oslo Univ Hosp, Inst Canc Genet & Informat, N-0316 Oslo, Norway

[15] Oslo Univ Hosp, Inst Canc Res, Dept Core Facil, N-0316 Oslo, Norway

[16] Natl Inst Environm Hlth Sci, Integrat Bioinformat Support Grp, Durham, NC 27709 USA

[17] Natl Inst Environm Hlth Sci, Genome Integr & Struct Biol Lab, Durham, NC 27709 USA

[18] Heidelberg Univ, Fac Biosci, D-69120 Heidelberg, Germany

[19] PROGETHER Prostate Canc Network, N-0316 Oslo, Norway

[20] Univ Med Ctr Hamburg Eppendorf, Martini Clin Prostate Canc Ctr, Martinistr 52, D-20246 Hamburg, Germany

[21] UT Southwestern Med Ctr, Dept Urol, Dallas, TX 75390 USA

[22] Ontario Inst Canc Res, Informat & Biocomp Program, Toronto, ON, Canada

[23] Natl Ctr Tumor Dis, NCT Trial Ctr, D-69120 Heidelberg, Germany

[24] German Canc Res Ctr, D-69120 Heidelberg, Germany

[25] German Canc Res Ctr, Bioinformat & Omics Data Analyt B240, D-69120 Heidelberg, Germany

[26] Univ Manchester, Manchester Canc Res Ctr, 555 Wilmslow Rd, Manchester, Lancs, England

[27] Ontario Inst Canc Res, Toronto, ON, Canada

[28] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada

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

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

[31] Charite Univ Med Berlin, Charitepl 1, D-10117 Berlin, Germany

来源：

CANCER CELL | 2018年 / 34卷 / 06期

关键词：

ANDROGEN RECEPTOR; DNA METHYLATION; GENE-EXPRESSION; MUTATIONAL PROCESSES; CELL; TRANSCRIPTION; GENOME; HETEROGENEITY; PROGRESSION; SIGNATURE;

D O I：

10.1016/j.ccell.2018.10.016

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Identifying the earliest somatic changes in prostate cancer can give important insights into tumor evolution and aids in stratifying high- from low-risk disease. We integrated whole genome, transcriptome and methylome analysis of early-onset prostate cancers (diagnosis <= 55 years). Characterization across 292 prostate cancer genomes revealed age-related genomic alterations and a clock-like enzymatic-driven mutational process contributing to the earliest mutations in prostate cancer patients. Our integrative analysis identified four molecular subgroups, including a particularly aggressive subgroup with recurrent duplications associated with increased expression of ESRP1, which we validate in 12,000 tissue microarray tumors. Finally, we combined the patterns of molecular co-occurrence and risk-based subgroup information to deconvolve the molecular and clinical trajectories of prostate cancer from single patient samples.

引用

页码：996 / +

页数：24

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