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

Am J Surg. 2016 Mar;211(3):506-11. doi: 10.1016/j.amjsurg.2015.11.002. Epub 2015 Dec 20.

Abstract

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.

Keywords: Genetic mutations; KRAS; Pancreas; Pancreatic cancer; TP53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / surgery*
  • Age Factors
  • Aged
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Molecular Medicine / methods*
  • Mutation*
  • Neoadjuvant Therapy
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / surgery*
  • Precision Medicine*
  • Prospective Studies
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Sequence Analysis, DNA / methods*
  • Sex Factors
  • Smad4 Protein / genetics

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • KRAS protein, human
  • SMAD4 protein, human
  • Smad4 Protein
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)