Next-generation sequencing in pancreatic cancer: Novel mutations and potential targets for therapy.

Journal of Clinical Oncology(2017)

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摘要
e15228 Background: Pancreatic adenocarcinoma (PA) has one of the worst prognoses of all malignancies prompting the search for oncogenic mutations that might be targets for therapy. Methods: We conducted a retrospective analysis of patients with PA who had next-generation sequencing (NGS). Key genes included were APC, ATM, BRAF, BRCA1, BRCA2, FLT3, NOTCH1, MET, FGFR4, MAPK1, MAP2K2, IDH1, IDH2, RET, JAK2, KRAS, NRAS, PTEN, EGFR, PIK3CA, PDGFRA, RUNX1, KIT, ALK, and TP53. Fluorescence in-situ hybridization (FISH) for EGFR gene amplification and MLL and ALK gene rearrangement was performed in a subset of patients. Variants were annotated with data incorporated from dbSNP, ClinVar and COSMIC. In-silico predictions were performed where applicable using PROVEAN (Protein Variation Effect Analyzer) and SIFT, and/or Polyphen (Polymorphism Phenotyping v2). Results: Among 45 patients with NGS, 31 patients (68.9%) had KRAS mutations and 14 patients (31.1%) were wild-type for KRAS. Of 29 patients whose tumors underwen...
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关键词
pancreatic cancer,novel mutations,next-generation
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