[PDF][PDF] Integrative clinical genomics of advanced prostate cancer

D Robinson, EM Van Allen, YM Wu, N Schultz… - Cell, 2015 - cell.com
D Robinson, EM Van Allen, YM Wu, N Schultz, RJ Lonigro, JM Mosquera, B Montgomery…
Cell, 2015cell.com
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 …
Summary
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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