Progress in cancer genetics: Lessons from pancreatic cancer

Research output: Contribution to journalArticle

Abstract

Background: In the near future advances in the molecular basis of cancer are expected to facilitate cancer diagnosis, to rationalize treatment, to facilitate screening, and to identify individuals requiring cancer prevention strategies. Methods: The literature was reviewed concerning the genetic alterations that contribute to pancreatic cancer development. Results: Virtually all pancreatic cancers have inactivation of the p16 pathway, and the majority inactivate the TGF beta/DPC4 and p53 tumor-suppressive pathways. Pancreatic cancers with mismatch repair deficiency have a characteristic histology and may have an improved prognosis. The recently discovered tumor suppressor genes, ALK-5, MKK4, and STK 11 (the gene responsible for Peutz- Jeghers syndrome) are all targeted for mutation in a small proportion of sporadic pancreatic cancers. Germline mutations of the BRCA2 gene are present in 5-10% of patients with pancreatic cancer. Typically such patients do not have a family history of pancreatic cancer and are mistaken as patients with sporadic disease. Five to 10% of patients with pancreatic cancer have first- degree relatives that will develop pancreatic cancer. Some such families also have a family history of melanoma and harbor germline p16 mutations. However, the gene(s) responsible for much of the inherited predisposition to pancreatic cancer remain to be identified. Conclusion: Further advances in pancreatic cancer molecular genetics are needed to facilitate the development of molecular screening tests, to identify additional familial susceptibility genes, and to identify targets for rational therapeutic targeting.

Original languageEnglish (US)
Pages (from-to)S4-S8
JournalAnnals of Oncology
Volume10
Issue numberSUPPL. 4
DOIs
StatePublished - Jan 1 1999

Keywords

  • ALK-5
  • BRCA2
  • DPC4
  • Mismatch repair
  • Pancreas cancer
  • Tumor suppressor genes
  • p16

ASJC Scopus subject areas

  • Hematology
  • Oncology

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