Description

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

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.

Reuse Permissions
  • Downloads
    PDF (1.9 MB)

    Details

    Title
    • Cancer of the Ampulla of Vater: Analysis of the Whole Genome Sequence Exposes a Potential Therapeutic Vulnerability
    Contributors
    Date Created
    2012-07-04
    Resource Type
  • Text
  • Collections this item is in
    Identifier
    • Digital object identifier: 10.1186/gm357
    • Identifier Type
      International standard serial number
      Identifier Value
      1756-994X
    Note
    • The electronic version of this article is the complete one and can be found online at: http://genomemedicine.biomedcentral.com/articles/10.1186/gm357

    Citation and reuse

    Cite this item

    This is a suggested citation. Consult the appropriate style guide for specific citation guidelines.

    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

    Machine-readable links