| Literature DB >> 29903880 |
Andrew J Aguirre1,2,3,4, Jonathan A Nowak5,4,6, Nicholas D Camarda5,2,7,8, Richard A Moffitt9, Arezou A Ghazani5,2,7, Mehlika Hazar-Rethinam10, Srivatsan Raghavan5,2,3,4, Jaegil Kim2, Lauren K Brais5, Dorisanne Ragon5, Marisa W Welch5, Emma Reilly5, Devin McCabe5,2,7,8, Lori Marini5,6,7, Kristin Anderka2, Karla Helvie5,7, Nelly Oliver5,7, Ana Babic5,4, Annacarolina Da Silva5,4,6, Brandon Nadres10, Emily E Van Seventer10, Heather A Shahzade10, Joseph P St Pierre5, Kelly P Burke5,3,4, Thomas Clancy5,4,11, James M Cleary5,3,4, Leona A Doyle5,4,6, Kunal Jajoo5,4,12, Nadine J McCleary5,3,4, Jeffrey A Meyerhardt5,3,4, Janet E Murphy10, Kimmie Ng5,3,4, Anuj K Patel5,3,4, Kimberly Perez5,3,4, Michael H Rosenthal5,4,13, Douglas A Rubinson5,3,4, Marvin Ryou5,4,12, Geoffrey I Shapiro5,3,4, Ewa Sicinska5,4, Stuart G Silverman5,4,13, Rebecca J Nagy14, Richard B Lanman14, Deborah Knoerzer15, Dean J Welsch15, Matthew B Yurgelun5,3,4, Charles S Fuchs5,4,7,8, Levi A Garraway5,2,3,4,7, Gad Getz2,4,10, Jason L Hornick5,4,6, Bruce E Johnson5,2,3,4,7, Matthew H Kulke5,3,4, Robert J Mayer5,3,4, Jeffrey W Miller8, Paul B Shyn5,4,13, David A Tuveson16, Nikhil Wagle5,2,3,4,7, Jen Jen Yeh17, William C Hahn5,2,3,4, Ryan B Corcoran4,10, Scott L Carter1,2,7,8, Brian M Wolpin1,3,4.
Abstract
Clinically relevant subtypes exist for pancreatic ductal adenocarcinoma (PDAC), but molecular characterization is not yet standard in clinical care. We implemented a biopsy protocol to perform time-sensitive whole-exome sequencing and RNA sequencing for patients with advanced PDAC. Therapeutically relevant genomic alterations were identified in 48% (34/71) and pathogenic/likely pathogenic germline alterations in 18% (13/71) of patients. Overall, 30% (21/71) of enrolled patients experienced a change in clinical management as a result of genomic data. Twenty-six patients had germline and/or somatic alterations in DNA-damage repair genes, and 5 additional patients had mutational signatures of homologous recombination deficiency but no identified causal genomic alteration. Two patients had oncogenic in-frame BRAF deletions, and we report the first clinical evidence that this alteration confers sensitivity to MAPK pathway inhibition. Moreover, we identified tumor/stroma gene expression signatures with clinical relevance. Collectively, these data demonstrate the feasibility and value of real-time genomic characterization of advanced PDAC.Significance: Molecular analyses of metastatic PDAC tumors are challenging due to the heterogeneous cellular composition of biopsy specimens and rapid progression of the disease. Using an integrated multidisciplinary biopsy program, we demonstrate that real-time genomic characterization of advanced PDAC can identify clinically relevant alterations that inform management of this difficult disease. Cancer Discov; 8(9); 1096-111. ©2018 AACR.See related commentary by Collisson, p. 1062This article is highlighted in the In This Issue feature, p. 1047. ©2018 American Association for Cancer Research.Entities:
Mesh：
Year: 2018 PMID： 29903880 PMCID： PMC6192263 DOI： 10.1158/2159-8290.CD-18-0275
Source DB: PubMed Journal: Cancer Discov ISSN： 2159-8274 Impact factor: 39.397