Using next-generation sequencing to determine potential molecularly guided therapy options for patients with resectable pancreatic adenocarcinoma.

American journal of surgery(2015)

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摘要
BACKGROUND:Genomic sequencing technology may identify personalized treatment options for patients with pancreatic adenocarcinoma. METHODS:The study was conducted using tissue specimens obtained from 2012 to 2014. Patients with resected pancreatic adenocarcinoma were identified. Next-generation sequencing was performed from paraffin-tumor blocks. Mutational profiles were reviewed to determine available targeted therapies and clinical trial eligibility. RESULTS:Thirty patients were identified. The incidence of mutations was: Kirsten rat sarcoma viral oncogene homolong (KRAS) = 87%, tumor protein 53 (TP53) = 63%, cyclin-dependent kinase inhibitor 2A (CDKN2A) = 20%, Mothers Against Decapentaplegic Homolog 4 (SMAD4) = 20%, epidermal growth factor receptor (EGFR) = 7%. Multiple mutations were found in 73%. All CDKN2A mutations occurred in male patients (P = .06), and there was a trend toward younger patient age in this group (P = .13). Potential for Federal Drug Administration (FDA)-approved targeted therapies was identified in 8 of 30 (27%). In addition, 29 of 30 (97%) had mutations applicable for ongoing phase I or II clinical trials. CONCLUSIONS:Next-generation sequencing of resected pancreatic adenocarcinoma specimens can determine common genetic mutations and identify patients who may be eligible for off-label use of targeted therapies or clinical trial enrollment.
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