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Integrative Clinical Genomics of Advanced Prostate Cancer

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

Prostate cancer

Biology

PTEN

2015

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.

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“Integrative Clinical Genomics of Advanced Prostate Cancer” is a paper by Dan R. Robinson Eliezer M. Van Allen Yi Wu Nikolaus Schultz Robert J. Lonigro Juan Miguel Mosquera Bruce Montgomery Mary Ellen Taplin Colin C. Pritchard Gerhardt Attard Himisha Beltran Wassim Abida Robert K. Bradley Jake Vinson Xuhong Cao Pankaj Vats Lakshmi P. Kunju Maha Hussain Felix Y. Feng Scott A. Tomlins Kathleen A. Cooney David C. Smith Christine Brennan Javed Siddiqui Rohit Mehra Yu Chen Dana E. Rathkopf Michael J. Morris Stephen B. Solomon Jeremy C. Durack Victor E. Reuter Anuradha Gopalan Jianjiong Gao Massimo Loda Rosina T. Lis Michaela Bowden Steve Balk Glenn C. Gaviola Carrie Sougnez Manaswi Gupta Evan Y. Yu Elahe A. Mostaghel Heather H. Cheng Hyojeong Mulcahy Lawrence D. True Stephen R. Plymate Heidi Dvinge Roberta Ferraldeschi Penny Flohr Susana Miranda Zafeiris Zafeiriou Nina Tunariu Joaquín Mateo Raquel Pérez-López Francesca Demichelis Brian D. Robinson Marc Schiffman David M. Nanus Scott T. Tagawa Alexandros Sigaras Kenneth Eng Olivier Elemento Andrea Sboner Elisabeth I. Heath Howard I. Scher Kenneth J. Pienta Philip W. Kantoff Mark A. Rubin Peter S. Nelson Levi A. Garraway Charles L. Sawyers Arul M. Chinnaiyan published in 2015. It has an Open Access status of “hybrid”. You can read and download a PDF Full Text of this paper here.