Molecular profiling of synchronous and metachronous cancers of the pancreas reveal molecular mimicry between samples from the same patient

Vanessa A. Talbott, Charles J. Yeo, Jonathan R. Brody, Agnieszka K. Witkiewicz

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Background: Pancreatic ductal adenocarcinoma (PDA) is rarely a survivable disease. In rare cases, separate synchronous tumors are discovered at the time of resection, while in others, patients present with a metachronous cancer after prior surgical resection. Studying molecular markers of synchronous and metachronous lesions may aid to clarify the biology of this often deadly disease. Methods: Two patients presented with synchronous tumors (each one with a tumor in the pancreatic head/neck and the other in the tail, designated patients A and B). An additional patient (patient C) underwent an R0 resection for PDA of the head and recurred 1.5 y later with PDA in the tail. Genomic DNA was laser capture microdissected (LCM) from the tumor and molecular analysis was performed. K-ras status and loss of heterozygosity (LOH) were determined from multiple specimens for each case. Results: All samples from each patient harbored identical K-ras mutations. In patient A, the tumor at the head of the pancreas had more clonal genetic instability as reflected by LOH analysis over multiple LCM samples. Patient B had more genetic instability in the tail lesion compared with the neck. Patient C had virtually the identical molecular profile in both tumors, supporting the notion that both tumors were related. Conclusion: We conclude that the synchronous and metachronous tumors likely are initiated from identical precursor lesions and/or events (i.e., K-ras mutations). Future studies will need to investigate if these tumors will respond similarly to adjuvant therapies targeted against the clonal molecular events in the tumor.

Original languageEnglish (US)
Pages (from-to)154-158
Number of pages5
JournalJournal of Surgical Research
Volume176
Issue number1
DOIs
StatePublished - Jul 1 2012

Keywords

  • metachronous tumors
  • molecular markers
  • multicentricity
  • pancreatic ductal adenocarcinoma
  • synchronous tumors

ASJC Scopus subject areas

  • Surgery

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