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Background: Recent advances in the treatment of cancer have focused on targeting genomic aberrations with selective therapeutic agents. In rare tumors, where large-scalec linical 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 DNAfrom a 63 year-old man who underwent a pancreaticoduodenectomy by whole genomesequencing, 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.
- Demeure, Michael J. (Author)
- Craig, David W. (Author)
- Sinari, Shripad (Author)
- Moses, Tracy M. (Author)
- Christoforides, Alexis (Author)
- Dinh, Jennifer (Author)
- Izatt, Tyler (Author)
- Aldrich, Jessica (Author)
- Decker, Ardis (Author)
- Baker, Angela (Author)
- Cherni, Irene (Author)
- Watanabe, April (Author)
- Koep, Lawrence (Author)
- Lake, Douglas (Author)
- Hostetter, Galen (Author)
- Trent, Jeffrey M. (Author)
- Von Hoff, Daniel D. (Author)
- Carpten, John D. (Author)
- College of Liberal Arts and Sciences (Contributor)
Demeure, M. J., Craig, D. W., Sinari, S., Moses, T. M., Christoforides, A., Dinh, J., . . . Carpten, J. D. (2012). Cancer of the ampulla of Vater: analysis of the whole genome sequence exposes a potential therapeutic vulnerability. Genome Medicine, 4(7), 56. doi:10.1186/gm357
- 2017-02-28 05:52:13
- 2021-10-26 11:31:24
- 3 years ago