Cancer of the ampulla of Vater: analysis of the whole genome sequence exposes a potential therapeutic vulnerability
1 Integrated Cancer Genomics Division, Translational Genomics Research Institute, 445 N. Fifth Ave, Phoenix, AZ 85004, USA
2 Virginia G Piper Cancer Center, 10290 N. 92nd St, Scottsdale, AZ 85258, USA
3 Neurogenomics Division, Translational Genomics Research Institute, 445 N. Fifth Ave, Phoenix, AZ 85004, USA
4 Clinical Translational Research Division, Translational Genomics Research Institute, 445 N. Fifth Ave, Phoenix, AZ 85004, USA
5 Department of Surgery, Banner Good Samaritan Medical Center, 1111 E. McDowell Rd, Phoenix, AZ 85006, USA
6 School of Life Sciences, Arizona State University, 427 E. Tyler Mall MC 5401 SOLS, Phoenix, AZ 85287, USA
Genome Medicine 2012, 4:56 doi:10.1186/gm357Published: 4 July 2012
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.
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.
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.
Whole genome sequencing can elucidate an oncogenic context and expose potential therapeutic vulnerabilities in rare cancers.