| Literature DB >> 26000489 |
Dan Robinson1, Eliezer M Van Allen2, Yi-Mi Wu1, Nikolaus Schultz3, Robert J Lonigro4, Juan-Miguel Mosquera5, Bruce Montgomery6, Mary-Ellen Taplin7, Colin C Pritchard8, Gerhardt Attard9, Himisha Beltran10, Wassim Abida11, Robert K Bradley12, Jake Vinson13, Xuhong Cao14, Pankaj Vats4, Lakshmi P Kunju15, Maha Hussain16, Felix Y Feng17, Scott A Tomlins18, Kathleen A Cooney16, David C Smith16, Christine Brennan4, Javed Siddiqui4, Rohit Mehra1, Yu Chen19, Dana E Rathkopf20, Michael J Morris20, Stephen B Solomon21, Jeremy C Durack21, Victor E Reuter22, Anuradha Gopalan22, Jianjiong Gao23, Massimo Loda24, Rosina T Lis25, Michaela Bowden26, Stephen P Balk27, Glenn Gaviola28, Carrie Sougnez29, Manaswi Gupta29, Evan Y Yu30, Elahe A Mostaghel6, Heather H Cheng6, Hyojeong Mulcahy31, Lawrence D True32, Stephen R Plymate30, Heidi Dvinge12, Roberta Ferraldeschi9, Penny Flohr9, Susana Miranda9, Zafeiris Zafeiriou9, Nina Tunariu9, Joaquin Mateo9, Raquel Perez-Lopez9, Francesca Demichelis33, Brian D Robinson5, Marc Schiffman34, David M Nanus10, Scott T Tagawa10, Alexandros Sigaras35, Kenneth W Eng35, Olivier Elemento36, Andrea Sboner37, Elisabeth I Heath38, Howard I Scher20, Kenneth J Pienta39, Philip Kantoff7, Johann S de Bono9, Mark A Rubin5, Peter S Nelson40, Levi A Garraway2, Charles L Sawyers41, Arul M Chinnaiyan42.
Abstract
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.Entities:
Mesh：
Year: 2015 PMID： 26000489 PMCID： PMC4484602 DOI： 10.1016/j.cell.2015.05.001
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582