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Molecular pathogenesis of exocrine pancreatic cancer

Ralph H Hruban, MD
Section Editor
Richard M Goldberg, MD
Deputy Editor
Diane MF Savarese, MD


Carcinoma of the exocrine pancreas is a genetic disease that is caused by inherited and acquired mutations in specific cancer-associated genes. Sequencing of the protein-coding exons from 20,661 genes in 24 advanced ductal adenocarcinomas of the pancreas provided the foundation for a more complete understanding of the key signaling pathways that are dysregulated in pancreatic tumorigenesis [1]. Additional whole-genome and whole-exome sequencing studies from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) have built on this foundation, and the genetics of pancreatic cancer are now well understood [2-4]. Progress in our understanding of the genes involved in the molecular pathogenesis of pancreatic cancer has provided insight into the familial aggregation of the disease and the progression of normal pancreatic cells to noninvasive precursor lesions and to invasive carcinoma, and has led to a new classification system of pancreatic neoplasms that encompasses both morphology and genetics [5-9].

As a general rule, multiple combinations of genetic mutations are commonly found in pancreatic adenocarcinomas [1-4]. These can be divided into three broad categories [10]:

Mutational activation of oncogenes such as KRAS

Inactivation of tumor suppressor genes such as TP53, p16/CDKN2A, and SMAD4

Inactivation of genome maintenance genes such as MLH1 and MSH2, which control the repair of DNA damage

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Literature review current through: Nov 2017. | This topic last updated: Nov 13, 2017.
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