Integrative clinical genomics of advanced prostate cancer.

Cell ·第 161 卷 ·第 5 期 ·2015-07-29

Robinson Dan, Van Allen Eliezer M, Wu Yi-Mi, Schultz Nikolaus, Lonigro Robert J, Mosquera Juan-Miguel, Montgomery Bruce, Taplin Mary-Ellen, Pritchard Colin C, Attard Gerhardt, Beltran Himisha, Abida Wassim, Bradley Robert K, Vinson Jake, Cao Xuhong, Vats Pankaj, Kunju Lakshmi P, Hussain Maha, Feng Felix Y, Tomlins Scott A, Cooney Kathleen A, Smith David C, Brennan Christine, Siddiqui Javed, Mehra Rohit, Chen Yu, Rathkopf Dana E, Morris Michael J, Solomon Stephen B, Durack Jeremy C, Reuter Victor E, Gopalan Anuradha, Gao Jianjiong, Loda Massimo, Lis Rosina T, Bowden Michaela, Balk Stephen P, Gaviola Glenn, Sougnez Carrie, Gupta Manaswi, Yu Evan Y, Mostaghel Elahe A, Cheng Heather H, Mulcahy Hyojeong, True Lawrence D, Plymate Stephen R, Dvinge Heidi, Ferraldeschi Roberta, Flohr Penny, Miranda Susana, Zafeiriou Zafeiris, Tunariu Nina, Mateo Joaquin, Perez-Lopez Raquel, Demichelis Francesca, Robinson Brian D, Schiffman Marc, Nanus David M, Tagawa Scott T, Sigaras Alexandros, Eng Kenneth W, Elemento Olivier, Sboner Andrea, Heath Elisabeth I, Scher Howard I, Pienta Kenneth J, Kantoff Philip, de Bono Johann S, Rubin Mark A, Nelson Peter S, Garraway Levi A, Sawyers Charles L, Chinnaiyan Arul M

摘要

Toward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole-exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%-60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF. Moreover, aberrations of BRCA2, BRCA1, and ATM were observed at substantially higher frequencies (19.3% overall) compared to those in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration, including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides clinically actionable information that could impact treatment decisions for these affected individuals.

文献信息

期刊

Cell

期刊简称

Cell

ISSN

0092-8674

发表日期

2015-07-29

收录日期

2015-05-24

更新日期

2016-11-22

语言

英语

国家/地区

United States

NLM ID

0413066

外部链接

PubMed 原文查看期刊详情

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Integrative clinical genomics of advanced prostate cancer.

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