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: Export Date: 2 July 2015 -- Source: Scopus
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MSK Authors
  1. Charles L Sawyers
    153 Sawyers
  2. Jacob Vinson
    6 Vinson
  3. Michael Morris
    274 Morris
  4. Yu Chen
    67 Chen
  5. Anuradha Gopalan
    273 Gopalan
  6. Stephen Solomon
    266 Solomon
  7. Dana Elizabeth Rathkopf
    142 Rathkopf
  8. Victor Reuter
    900 Reuter
  9. Howard Scher
    817 Scher
  10. Jianjiong Gao
    62 Gao
  11. Wassim Abida
    36 Abida
  12. Nikolaus D Schultz
    196 Schultz
  13. Jeremy Charles Durack
    84 Durack