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Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine
- Source :
- Cancer Discovery. 8:1096-1111
- Publication Year :
- 2018
- Publisher :
- American Association for Cancer Research (AACR), 2018.
-
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. 1062. This article is highlighted in the In This Issue feature, p. 1047
- Subjects :
- Adult
Male
0301 basic medicine
DNA Repair
MAP Kinase Signaling System
DNA repair
Germline
03 medical and health sciences
0302 clinical medicine
Germline mutation
Pancreatic cancer
Exome Sequencing
Carcinoma
medicine
Humans
Gene Regulatory Networks
Clinical significance
Precision Medicine
Homologous Recombination
Germ-Line Mutation
Exome sequencing
Aged
Aged, 80 and over
Sequence Analysis, RNA
business.industry
Gene Expression Profiling
Genetic Variation
Genomics
Middle Aged
medicine.disease
Precision medicine
Gene Expression Regulation, Neoplastic
Pancreatic Neoplasms
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Cancer research
Female
business
Carcinoma, Pancreatic Ductal
Subjects
Details
- ISSN :
- 21598290 and 21598274
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Cancer Discovery
- Accession number :
- edsair.doi.dedup.....162e493848359d962fcc66f34433fe3d