1. Integrative Clinical Genomics of Advanced Prostate Cancer
- Author
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Yi-Mi Wu, Glenn C. Gaviola, Massimo Loda, Scott A. Tomlins, Raquel Perez-Lopez, Bruce Montgomery, Himisha Beltran, Jeremy C. Durack, Mary-Ellen Taplin, Michael J. Morris, David Smith, Charles L. Sawyers, Arul M. Chinnaiyan, Penny Flohr, Anuradha Gopalan, Howard I. Scher, Christine Brennan, Carrie Sougnez, Scott T. Tagawa, Roberta Ferraldeschi, Rohit Mehra, Stephen P. Balk, Manaswi Gupta, Eliezer M. Van Allen, Philip W. Kantoff, Rosina T. Lis, Evan Y. Yu, Jianjiong Gao, Kenneth J. Pienta, Xuhong Cao, Joaquin Mateo, Johann S. de Bono, Maha Hussain, Olivier Elemento, Stephen B. Solomon, Zafeiris Zafeiriou, Robert J. Lonigro, Wassim Abida, Hyojeong Mulcahy, Jake Vinson, Gerhardt Attard, Andrea Sboner, Nina Tunariu, Javed Siddiqui, Yu Chen, Michaela Bowden, Colin C. Pritchard, Lakshmi P. Kunju, Susana Miranda, Lawrence D. True, Felix Y. Feng, Heather H. Cheng, Kathleen A. Cooney, Peter S. Nelson, Francesca Demichelis, Pankaj Vats, Dan R. Robinson, Brian D. Robinson, Marc H. Schiffman, Mark A. Rubin, Kenneth Eng, Juan Miguel Mosquera, Stephen R. Plymate, Elahe A. Mostaghel, Robert K. Bradley, Alexandros Sigaras, Elisabeth I. Heath, Nikolaus Schultz, Heidi Dvinge, Victor E. Reuter, Dana E. Rathkopf, Levi A. Garraway, and David M. Nanus
- Subjects
Male ,Oncology ,medicine.medical_specialty ,Bioinformatics ,General Biochemistry, Genetics and Molecular Biology ,Cohort Studies ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Prostate ,Internal medicine ,medicine ,Humans ,PTEN ,Neoplasm Metastasis ,030304 developmental biology ,0303 health sciences ,biology ,Biochemistry, Genetics and Molecular Biology(all) ,Gene Expression Profiling ,Precision medicine ,medicine.disease ,3. Good health ,Gene expression profiling ,Prostatic Neoplasms, Castration-Resistant ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Mutation ,Cohort ,biology.protein ,Cancer biomarkers ,Cohort study - Abstract
SummaryToward 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.
- Published
- 2015