Integrative clinical genomics of advanced prostate cancer Journal Article
| Authors: | Robinson, D.; Van Allen, E. M.; Wu, Y. M.; Schultz, N.; Lonigro, R. J.; Mosquera, J. M.; Montgomery, B.; Taplin, M. E.; Pritchard, C. C.; Attard, G.; Beltran, H.; Abida, W.; Bradley, R. K.; Vinson, J.; Cao, X.; Vats, P.; Kunju, L. P.; Hussain, M.; Feng, F. Y.; Tomlins, S. A.; Cooney, K. A.; Smith, D. C.; Brennan, C.; Siddiqui, J.; Mehra, R.; Chen, Y.; Rathkopf, D. E.; Morris, M. J.; Solomon, S. B.; Durack, J. C.; Reuter, V. E.; Gopalan, A.; Gao, J.; Loda, M.; Lis, R. T.; Bowden, M.; Balk, S. P.; Gaviola, G.; Sougnez, C.; Gupta, M.; Yu, E. Y.; Mostaghel, E. A.; Cheng, H. H.; Mulcahy, H.; True, L. D.; Plymate, S. R.; Dvinge, H.; Ferraldeschi, R.; Flohr, P.; Miranda, S.; Zafeiriou, Z.; Tunariu, N.; Mateo, J.; Perez-Lopez, R.; Demichelis, F.; Robinson, B. D.; Schiffman, M.; Nanus, D. M.; Tagawa, S. T.; Sigaras, A.; Eng, K. W.; Elemento, O.; Sboner, A.; Heath, E. I.; Scher, H. I.; Pienta, K. J.; Kantoff, P.; de Bono, J. S.; Rubin, M. A.; Nelson, P. S.; Garraway, L. A.; Sawyers, C. L.; Chinnaiyan, A. M. |
| Article Title: | Integrative clinical genomics of advanced prostate cancer |
| 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. © 2015 Elsevier Inc. |
| Keywords: | signal transduction; bone tumor; missense mutation; histopathology; advanced cancer; medical decision making; cell cycle; dna repair; metastasis; cohort analysis; tumor biopsy; brca1 protein; brca2 protein; protein p53; chromosome aberration; atm protein; genomics; decision making; tumor gene; beta catenin; transcriptome; b raf kinase; apc protein; soft tissue tumor; genetic counseling; castration resistant prostate cancer; clinical trial (topic); germline mutation; wnt signaling pathway; exome; human; male; priority journal; article |
| Journal Title: | Cell |
| Volume: | 161 |
| Issue: | 5 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2015-05-21 |
| Start Page: | 1215 |
| End Page: | 1228 |
| Language: | English |
| DOI: | 10.1016/j.cell.2015.05.001 |
| PROVIDER: | scopus |
| PMCID: | PMC4484602 |
| PUBMED: | 26000489 |
| DOI/URL: | |
| Notes: | Erratum issued, see DOI: [10.1016/j.cell.2015.06.053] -- Source: Scopus |
