Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine
Top Cited Papers
Open Access
- 1 September 2018
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Cancer Discovery
- Vol. 8 (9), 1096-1111
- https://doi.org/10.1158/2159-8290.CD-18-0275
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. (C) 2018 AACR.Other Versions
Funding Information
- Lustgarten Foundation
- Noble Effort Fund
- Peter R. Leavitt Family Fund
- Wexler Family Fund
- Promises for Purple
- HHS | NIH | National Cancer Institute (NCI) (P50CA127003)
- HHS | NIH | National Cancer Institute (NCI) (U01CA224146)
- HHS | NIH | National Cancer Institute (NCI) (U01CA210171)
- HHS | NIH | National Cancer Institute (NCI) (R01CA199064)
- Pancreatic Cancer Action Network (PanCAN)
- Hale Center for Pancreatic Cancer Research, Dana-Farber Cancer Institute
- Hope Funds for Cancer Research
- Doris Duke Charitable Foundation (DDCF)
- Conquer Cancer Foundation (CCF)
- HHS | NIH | National Cancer Institute (NCI) (K08CA2118420-01)
- Broman Fund for Pancreatic Cancer Research
- Harvard Clinical and Translational Sciences Center (UL1 TR001102)
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