Year: 2023
Type: other
Abstract: There has been a revolution in our understanding of the molecular drivers of cystic neoplasms of the pancreas. All of the major types of cystic neoplasms of the pancreas have been sequenced, and, remarkably, each cyst type appears to have its own unique mutational profile. The VHL gene is targeted for inactivation in serous cystic neoplasms. The KRAS , RNF43 , PIK3CA , p16/CDKN2A , SMAD4 , and TP53 genes are targeted both in intraductal papillary mucinous neoplasms (IPMN) and in mucinous cystic neoplasms, while GNAS is targeted only in IPMN. Virtually all solid pseudopapillary neoplasms harbor beta-catenin ( CTNNB1 ) gene mutations. Some genetic changes, such as KLF4 mutations appear to be indicators of low-grade lesions, while SMAD4 and TP53 inactivation, and aneuploidy appear to be markers of high-grade dysplasia in IPMN. Intraductal oncocytic papillary neoplasms harbor specific translocations. Distinctive patterns of DNA methylation, and of microRNA, mRNA, and protein expression have also been described in some cyst types. This improved understanding of the molecular drivers of cystic neoplasms of the pancreas is now being applied to improving patient care. For example, cyst fluid can be aspirated from a pancreatic cyst at the time of endoscopic ultrasound, and nucleic acids isolated from the fluid can then be tested for the presence of genetic and epigenetic alterations, providing information on the cyst type, and, in some cases, the likely degree of dysplasia, as well as revealing the presence of actionable genetic alterations.
Authors: Nickolas Papadopoulos, Ralph H. Hruban
Institutions: Johns Hopkins University, Johns Hopkins Medicine
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4385567299