title: Cancer of the ampulla of Vater: analysis of the whole genome sequence exposes a potential therapeutic vulnerability.
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 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.
authors: Integrated Cancer Genomics Division, Translational Genomics Research Institute, 445 N. Fifth Ave, Phoenix, AZ 85004, USA ; Virginia G Piper Cancer Center, 10290 N. 92nd St, Scottsdale, AZ 85258, USA.
authors: Michael J
authors: MJ
authors: Demeure
authors: Neurogenomics Division, Translational Genomics Research Institute, 445 N. Fifth Ave, Phoenix, AZ 85004, USA.
authors: David W
authors: DW
authors: Craig
authors: Neurogenomics Division, Translational Genomics Research Institute, 445 N. Fifth Ave, Phoenix, AZ 85004, USA.
authors: Shripad
authors: S
authors: Sinari
authors: Integrated Cancer Genomics Division, Translational Genomics Research Institute, 445 N. Fifth Ave, Phoenix, AZ 85004, USA.
authors: Tracy M
authors: TM
authors: Moses
authors: Neurogenomics Division, Translational Genomics Research Institute, 445 N. Fifth Ave, Phoenix, AZ 85004, USA.
authors: Alexis
authors: A
authors: Christoforides
authors: Integrated Cancer Genomics Division, Translational Genomics Research Institute, 445 N. Fifth Ave, Phoenix, AZ 85004, USA.
authors: Jennifer
authors: J
authors: Dinh
authors: Neurogenomics Division, Translational Genomics Research Institute, 445 N. Fifth Ave, Phoenix, AZ 85004, USA.
authors: Tyler
authors: T
authors: Izatt
authors: Neurogenomics Division, Translational Genomics Research Institute, 445 N. Fifth Ave, Phoenix, AZ 85004, USA.
authors: Jessica
authors: J
authors: Aldrich
authors: Clinical Translational Research Division, Translational Genomics Research Institute, 445 N. Fifth Ave, Phoenix, AZ 85004, USA.
authors: Ardis
authors: A
authors: Decker
authors: Integrated Cancer Genomics Division, Translational Genomics Research Institute, 445 N. Fifth Ave, Phoenix, AZ 85004, USA.
authors: Angela
authors: A
authors: Baker
authors: Integrated Cancer Genomics Division, Translational Genomics Research Institute, 445 N. Fifth Ave, Phoenix, AZ 85004, USA.
authors: Irene
authors: I
authors: Cherni
authors: Integrated Cancer Genomics Division, Translational Genomics Research Institute, 445 N. Fifth Ave, Phoenix, AZ 85004, USA.
authors: April
authors: A
authors: Watanabe
authors: Department of Surgery, Banner Good Samaritan Medical Center, 1111 E. McDowell Rd, Phoenix, AZ 85006, USA.
authors: Lawrence
authors: L
authors: Koep
authors: School of Life Sciences, Arizona State University, 427 E. Tyler Mall MC 5401 SOLS, Phoenix, AZ 85287, USA.
authors: Douglas
authors: D
authors: Lake
authors: Integrated Cancer Genomics Division, Translational Genomics Research Institute, 445 N. Fifth Ave, Phoenix, AZ 85004, USA.
authors: Galen
authors: G
authors: Hostetter
authors: Integrated Cancer Genomics Division, Translational Genomics Research Institute, 445 N. Fifth Ave, Phoenix, AZ 85004, USA.
authors: Jeffrey M
authors: JM
authors: Trent
authors: Virginia G Piper Cancer Center, 10290 N. 92nd St, Scottsdale, AZ 85258, USA ; Clinical Translational Research Division, Translational Genomics Research Institute, 445 N. Fifth Ave, Phoenix, AZ 85004, USA.
authors: Daniel D
authors: DD
authors: Von Hoff
authors: Integrated Cancer Genomics Division, Translational Genomics Research Institute, 445 N. Fifth Ave, Phoenix, AZ 85004, USA.
authors: John D
authors: JD
authors: Carpten