Real-time genomic profiling of pancreatic ductal adenocarcinoma: Potential actionability and correlation with clinical phenotype Journal Article

Authors: Lowery, M. A.; Jordan, E. J.; Basturk, O.; Ptashkin, R. N.; Zehir, A.; Berger, M. F.; Leach, T.; Herbst, B.; Askan, G.; Maynard, H.; Glassman, D.; Covington, C.; Schultz, N.; Abou-Alfa, G. K.; Harding, J. J.; Klimstra, D. S.; Hechtman, J. F.; Hyman, D. M.; Allen, P. J.; Jarnagin, W. R.; Balachandran, V. P.; Varghese, A. M.; Schattner, M. A.; Yu, K. H.; Saltz, L. B.; Solit, D. B.; Iacobuzio-Donahue, C. A.; Leach, S. D.; O'Reilly, E. M.
Article Title: Real-time genomic profiling of pancreatic ductal adenocarcinoma: Potential actionability and correlation with clinical phenotype
Abstract: Purpose: Molecular profiling in cancer has identified potential actionable drug targets that have prompted attempts to discover clinically validated biomarkers to guide therapeutic decision-making and enrollment to clinical trials. We evaluated whether comprehensive genetic analysis of patients with pancreatic adenocarcinoma is feasible within a clinically relevant timeframe and whether such analyses provide predictive and/or prognostic information along with identification of potential targets for therapy. Experimental Design: Archival or prospectively acquired FFPE samples and matched normal DNA from N = 336 patients with pancreatic cancer were analyzed using a hybridization capture-based, next-generation sequencing assay designed to perform targeted deep sequencing of all exons and selected introns of 410 key cancer-associated genes. Demographic and treatment data were prospectively collected with the goal of correlating treatment outcomes and drug response with molecular profiles. Results: The median time from protocol consent to reporting of the genomic results was 45 days with a median time from tissue delivery of 20 days. All genetic alterations identified were stratified based upon prior evidence that the mutation is a predictive biomarker of drug response using the MSKCC OncoKB classification. Three of 225 patients (1%) received a matched therapy based upon the sequencing results. Conclusions: The practical application of molecular results to guide individual patient treatment is currently limited in patients with pancreatic adenocarcinoma. Future prospective molecular profiling efforts should seek to incorporate routine germline genetic analysis and the identification of DNA profiles that predict for clinical benefit from agents that target DNA damage repair and or immunotherapy. (C) 2017 AACR.
Keywords: mutations; cancer
Journal Title: Clinical Cancer Research
Volume: 23
Issue: 20
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2017-10-15
Start Page: 6094
End Page: 6100
Language: English
ACCESSION: WOS:000413151000012
DOI: 10.1158/1078-0432.ccr-17-0899
PUBMED: 28754816
Notes: Article -- Source: Wos
Citation Impact
MSK Authors
  1. Leonard B Saltz
    664 Saltz
  2. David Solit
    537 Solit
  3. Olca Basturk
    233 Basturk
  4. James Joseph Harding
    106 Harding
  5. Ghassan Abou-Alfa
    302 Abou-Alfa
  6. David S Klimstra
    911 Klimstra
  7. Maeve Aine Lowery
    128 Lowery
  8. Peter Allen
    475 Allen
  9. Kenneth Ho-Ming Yu
    96 Yu
  10. William R Jarnagin
    640 Jarnagin
  11. David Hyman
    299 Hyman
  12. Ahmet Zehir
    212 Zehir
  13. Eileen O'Reilly
    421 O'Reilly
  14. Michael Forman Berger
    495 Berger
  15. Mark Schattner
    114 Schattner
  16. Nikolaus D Schultz
    258 Schultz
  17. Jaclyn Frances Hechtman
    160 Hechtman
  18. Steven Leach
    30 Leach
  19. Gokce Askan
    59 Askan
  20. Emmet John Jordan
    43 Jordan
  21. Tanisha N Leach
    1 Leach
  22. Brian Thomas Herbst
    4 Herbst