Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pancreatic intraepithelial neoplasia (PanIN) is a precursor to invasive ductal adenocarcinoma of the pancreas. Observations made in genetically engineered mouse models suggest that the acinar/centroacinar compartment can give rise to ductal neoplasia. To integrate findings in mice and men, we examined human acinar cells, acinar-ductal metaplasia (ADM) lesions, and PanINs for KRAS2 gene mutations. Surgically resected pancreata were screened for foci of ADM with or without an associated PanIN lesion. Stromal cells, acinar cells, ADMs, and PanINs were separately isolated using laser capture microdissection. KRAS2 status was analyzed using genomic DNA isolated from the microdissected tissue. Twelve of these 31 foci of ADM occurred in isolation, whereas 19 were in the same lobules as a PanIN lesion. All 31 microdissected foci of acinar cells were KRAS2 gene wild-type, as were all 12 isolated ADM lesions lacking an associated PanIN. KRAS2 gene mutations were present in 14 of 19 (74%) PanIN lesions and in 12 of the 19 (63%) foci of ADM associated with these PanINs. All ADM lesions with a KRAS2 gene mutation harbored the identical KRAS2 gene mutation found in their associated PanIN lesions. Ductal neoplasms of the human pancreas, as defined by KRAS2 gene mutations, do not appear to arise from acinar cells. Isolated AMD lesions are genetically distinct from those associated with PanINs, and the latter may represent retrograde extension of the neoplastic PanIN cells or less likely are precursors to PanIN.
Mol Cancer Res 2009 Feb
PMID:KRAS2 mutations in human pancreatic acinar-ductal metaplastic lesions are limited to those with PanIN: implications for the human pancreatic cancer cell of origin. 1920 45

Precursor lesions of pancreatic cancer have been recognized about a century ago. The development of a consistent reproducible nomenclature and classification system for these lesions has been a major advance in the study of these noninvasive precursors. Pancreatic intraepithelial neoplasia (PanIN) as microscopic precursor lesions can be distinguished from mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMN) that are cystic and can often be recognized on imaging. Since precursor lesions harbor the unique chance to treat a patient before a fatal pancreatic cancer can arise a molecular characterization is essential to understand the biology and to find diagnostic and therapeutic targets to fight this disease of near uniform lethality. In order to study precursor lesions on a molecular level a meticulous isolation of the neoplastic cells is inevitable. We present the salient histopathologic and molecular features of precursor lesions of pancreatic cancer as well as methods that have proved to be useful within experimental studies.
Methods Mol Biol 2013
PMID:Identification and analysis of precursors to invasive pancreatic cancer. 2335 46