Cancer of the ampulla of Vater: Analysis of the whole genome sequence exposes a potential therapeutic vulnerability

Michael J. Demeure, David W. Craig, Shripad Sinari, Tracy M. Moses, Alexis Christoforides, Jennifer Dinh, Tyler Izatt, Jessica Aldrich, Ardis Decker, Angela Baker, Irene Cherni, April Watanabe, Lawrence Koep, Douglas Lake, Galen Hostetter, Jeffrey M. Trent, Daniel D. Von Hoff, John D. Carpten

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Background: Recent advances in the treatment of cancer have focused on targeting genomic aberrations with selective therapeutic agents. In rare tumors, where large-scale clinical trials are daunting, this targeted genomic approach offers a new perspective and hope for improved treatments. Cancers of the ampulla of Vater are rare tumors that comprise only about 0.2% of gastrointestinal cancers. Consequently, they are often treated as either distal common bile duct or pancreatic cancers.Methods: We analyzed DNA from a resected cancer of the ampulla of Vater and whole blood DNA from a 63 year-old man who underwent a pancreaticoduodenectomy by whole genome sequencing, achieving 37× and 40× coverage, respectively. We determined somatic mutations and structural alterations.Results: We identified relevant aberrations, including deleterious mutations of KRAS and SMAD4 as well as a homozygous focal deletion of the PTEN tumor suppressor gene. These findings suggest that these tumors have a distinct oncogenesis from either common bile duct cancer or pancreatic cancer. Furthermore, this combination of genomic aberrations suggests a therapeutic context for dual mTOR/PI3K inhibition.Conclusions: Whole genome sequencing can elucidate an oncogenic context and expose potential therapeutic vulnerabilities in rare cancers.

Original languageEnglish (US)
Article number56
JournalGenome Medicine
Issue number7
StatePublished - Jul 4 2012

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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