This section shows a summary for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.
- Cancer of the ampulla of Vater: analysis of the whole genome sequence exposes a potential therapeutic vulnerability.
- Paper ID
Genome medicine, 2012;4(7):56
PMID: 22762308 (view at PubMed or Europe PMC)
- ABSTRACT: 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 a 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 40x 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 than 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.
- Paper Status