Pancreatic Cancer: Molecular Genetics and Clinical Applications


Pancreatic cancer (PC) is a relatively common type of cancer with a dismal prognosis. Recent advances in molecular biology allowed the identification of many of the genes involved in pancreatic carcinogenesis; currently, it is accepted that PC is fundamentally a genetic disease caused by inherited and acquired (somatic) mutations in cancer‐associated genes (oncogenes, tumour‐suppressor genes, genome‐maintenance genes). Other genetic/molecular pathways (such as telomere shortening, upregulation and overexpression of growth factors or their receptors (such as EGFR, TGFβ), tumour angiogenesis and alterations of developmental signalling pathways (such as the Hedgehog signalling pathway)) are also involved in pancreatic carcinogenesis. Pancreatic carcinogenesis is a multistep phenomenon, characterised by the progressive accumulation of multiple genetic alterations, which occur in an ordered sequence rather than a random fashion. Advances in our understanding of molecular biology of PC will improve clinical management of patients with PC by providing better diagnostic, prognostic and therapeutic tools.

Key Concepts:

  • Pancreatic cancer has been associated with inherited and acquired (somatic) mutations in cancer‐related genes.

  • Genes involved in pancreatic carcinogenesis include oncogenes, tumour‐suppressor genes and genome‐maintenance genes.

  • Other genetic/molecular pathways are also involved in pancreatic carcinogenesis, such as telomere shortening, developmental signalling pathways (such as the Hedgehog signalling pathway), and upregulation and overexpression of growth factors or their receptors (such as EGFR, TGFβ, VEGF‐A, VEGFR1, VEGFR2).

  • Pancreatic carcinogenesis is a multistep phenomenon, characterised by the progressive accumulation of multiple genetic/molecular alterations, occurring in an ordered sequence rather than a random fashion.

  • Potential clinical implications include the recognition of groups of individuals with high risk for PC development (in these groups an as yet undefined programme of intensive surveillance may diagnose pancreatic lesions at a pre‐invasive stage) and the development of new and effective diagnostic, prognostic and therapeutic tools.

Keywords: pancreas; cancer; molecular biology; genes; oncogenes; surgery; management; diagnosis; treatment

Figure 1.

Multistep pancreatic carcinogenesis. Note the progression of pancreatic neoplasia from premalignant pancreatic lesions (PanIN, left) to carcinoma (right). (From Maitra et al., .)



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Sakorafas, George H, Pappa, Irene, and Smyrniotis, Vasileios(Dec 2010) Pancreatic Cancer: Molecular Genetics and Clinical Applications. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0006057.pub2]