Very long-term survival following resection for pancreatic cancer is not explained by commonly mutated genes: Results of whole-exome sequencing analysis

Marco Dal Molin, Ming Zhang, Roeland F. De Wilde, Niki A. Ottenhof, Neda Rezaee, Christopher L. Wolfgang, Amanda Blackford, Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Ralph H. Hruban, Anirban Maitra, Laura D. Wood

Research output: Contribution to journalArticle

Abstract

Purpose: The median survival following surgical resection of pancreatic ductal adenocarcinoma (PDAC) is currently <20 months. However, survival ≥10 years is achieved by a small subset of patients who are defined as very long-term survivors (VLTS). The goal of this study was to determine whether specific genetic alterations in resected PDACs determined very long-term survival. Experimental Design: We sequenced the exomes of eight PDACs from patients who survived ≥10 years. On the basis of the results of the exomic analysis, targeted sequencing of selected genes was performed in a series of 27 additional PDACs from VLTSs. Results: KRAS mutations were identifi ed in 33 of 35 cancers (94%) from VLTSs and represented the most prevalent alteration in our cohort. TP53, SMAD4, and CDKN2A mutations occurred in 69%, 26%, and 17%, respectively. Mutations in RNF43, which have been previously associated with intraductal papillary mucinous neoplasms, were identifi ed in four of the 35 cancers (11%). Taken together, our data show no difference in somatic mutations in carcinomas from VLTSs compared with available data from PDACs unselected for survival. Comparison of clinicopathologic features between VLTSs and a matching control group demonstrated that younger age, earlier stage, well/moderate grade of differentiation, and negative resection margins were associated with VLTS. However, more advanced stage, poor grade, or nodal disease did not preclude long-term survival. Conclusions: Our results suggest that in most patients, somatic mutations in commonly mutated genes are unlikely to be the primary determinant of very long-term survival following surgical resection of PDAC.

Original languageEnglish (US)
Pages (from-to)1944-1950
Number of pages7
JournalClinical Cancer Research
Volume21
Issue number8
DOIs
StatePublished - Apr 15 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Very long-term survival following resection for pancreatic cancer is not explained by commonly mutated genes: Results of whole-exome sequencing analysis'. Together they form a unique fingerprint.

  • Cite this