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pancreatic adenocarcinoma

Wednesday 29 October 2003

exocrine pancreatic cancer, pancreatic adenocarcinomas, pancreatic cancer; pancreas cancer

Digital case

- JRC:10443 : cutaneous metastasis of a pancreatic adenocarcinoma.

Definition: Pancreatic adenocarcinoma is the fifth leading cause of cancer death with a 5-year survival rate of less than 5%.

Molecular biology

Although the role of a few known oncogenes and tumor suppressor genes in the development of pancreatic cancer is fairly well established, it is obvious that the majority of genetic changes responsible for the initiation and progression of this disease are still unknown.

- genic inactivations by somatic mutations

  • p53 (TP53) at 17p13.1 (MIM.191170)
  • p16 (CDKN2A or MTS1) at 9p21 (MIM.600160)
  • MADH4 (DPC4 or SMAD4) at 18q21.1 (MIM.600993)
  • ACVR1B at 12q13 (MIM.601300)

- genic activation

  • K-RAS (KRAS2) at 12q12.1 (MIM.190070)

Susceptibility loci

- 21q21.3 (22158540)
- 5p13.1 (22158540)
- 21q22.3 (22158540)
- 22q13.32 (22158540)
- 10q26.11 (22158540)

Familial predisposition

Familial pancreatic cancer (FPC) represents 9% of PC, and the risk of malignancy in kindred does not appear to be confined to the pancreas. (25313458)

Genetic risk factors are believed to play a major role. Approximately 10% of PC is estimated to have familial inheritance.

Several germline mutations have been found to be involved in hereditary forms of PC, including both familial PC (FPC) and PC as one of the manifestations of a hereditary cancer syndrome or other hereditary conditions.

Candidate genes have been described and patients considered for screening programs under research protocols should first be tested for presence of germline mutations in the BRCA2, PALB2 and ATM genes. In specific PC populations, including in Italy, hereditary cancer predisposition genes such as CDKN2A also explain a considerable fraction of FPC. (25152581)

Candidate genes: BRCA2, PALB2, ATM, CDKN2A. (25152581)

See: familial pancreatic cancer

Links

- Nomenclature for Classification of Duct Lesions in the Pancreas (NCI, 1999) at Hopkins

Videos

- Pancreatic adenocarcinoma by Washington Deceit (1)

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- Pancreatic adenocarcinoma by Washington Deceit (2)

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Reviews

- Welsch T, Kleeff J, Friess H. Molecular pathogenesis of pancreatic cancer: advances and challenges. Curr Mol Med. 2007 Aug;7(5):504-21. PMID: 17691965

- Karhu R, Mahlamaki E, Kallioniemi A. Pancreatic adenocarcinoma — genetic portrait from chromosomes to microarrays. Genes Chromosomes Cancer. 2006 Aug;45(8):721-30. PMID: 16688744

- Soto JL, Barbera VM, Saceda M, Carrato A. Molecular biology of exocrine pancreatic cancer. Clin Transl Oncol. 2006 May;8(5):306-12. PMID: 16760004

- Laheru D, Jaffee EM. Immunotherapy for pancreatic cancer - science driving clinical progress. Nat Rev Cancer. 2005 Jun;5(6):459-67. PMID: 15905855

- Lynch HT, Deters CA, Lynch JF, Brand RE. Familial pancreatic carcinoma in Jews. Fam Cancer. 2004;3(3-4):233-40. PMID: 15516847

- Hilgers W, Rosty C, Hahn SA. Molecular pathogenesis of pancreatic cancer. Hematol Oncol Clin North Am. 2002 Feb;16(1):17-35, v. PMID: 12063826

- Bardeesy N, DePinho RA. Pancreatic cancer biology and genetics. Nat Rev Cancer. 2002 Dec;2(12):897-909. PMID: 12459728

References

- Genome-wide association study identifies five loci associated with susceptibility to pancreatic cancer in Chinese populations. Wu C, Miao X, Huang L, Che X, Jiang G, Yu D, Yang X, Cao G, Hu Z, Zhou Y, Zuo C, Wang C, Zhang X, Zhou Y, Yu X, Dai W, Li Z, Shen H, Liu L, Chen Y, Zhang S, Wang X, Zhai K, Chang J, Liu Y, Sun M, Cao W, Gao J, Ma Y, Zheng X, Cheung ST, Jia Y, Xu J, Tan W, Zhao P, Wu T, Wang C, Lin D. Nat Genet. 2011 Dec 11;44(1):62-6. PMID: 22158540