Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Pancreatic Carcinoma [C25.-]

OMIM numbers: 260350KRAS (190070), GNAS (139320)

Dipl.-Ing. (FH) Tanja Hinrichsen,
Prof. Dr. med. Barbara Dockhorn-Dworniczak

Scientific Background

Pancreatic carcinoma has the lowest survival rate of all cancers and is the fourth most common cause of cancer deaths. Since the formation of malignant neoplasms in the pancreas often causes no symptoms or only nonspecific symptoms in the early stages, the tumor is often diagnosed late, meaning that the relative 5-year survival rate in Germany for both men and women is about 8%. Rare malignant islet cell tumors have a much better prognosis. Tumors of the exocrine pancreas make up about 95% of cases and tumors of the endocrine pancreas about 5% of cases.

Three precursors to pancreatic cancer have been described. The majority of pancreatic tumors develop from pancreatic intraepithelial neoplasia (PanIN), which are further divided according to their degree of morphological atypia into PanIN 1, PanIN 2 and PanIN 3. Nearly all PanIN have mutations in KRAS and can accumulate further mutations in CDKN2A, TP53, SMAD4 and BRCA2. In addition, intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN) may also have mutations in the above mentioned genes. Unlike PanIN, IPMN and MCN are often macroscopically detectable by conventional imaging techniques. However, it is not possible to distinguish these lesions from other benign lesions, or from one another without resection and histological evaluation.

High throughput studies have shown only the presence of entity specific changes. Thus, mutations in GNAS codon 201 occur only in IPMN (41-66%), but not in MCN, serous cystadenoma (SCA) or solid pseudopapillary neoplasms (SPN). Hence, the use of tumor cystic fluid for preoperative diagnosis and GNAS mutation analysis.