Molecular diagnosis of pancreas carcinoma.
Cellular protooncogenes, tumor suppressor genes (antioncogenes), and DNA mismatch repair mutators are generally the key molecular genetic biomarkers undergoing alterations during carcinogenesis, i.e., activation of oncogenes, inactivation of tumor suppressors, and DNA mismatch repair gene defects are essential events in cancer causation. In pancreas cancer, high incidence of oncogene K-ras point mutations at the codon 12th is associated with premalignant and malignant transformation. Mutation in p53 tumor suppressor is also detected in pancreas adenocarcinoma. Concurrent loss of p53 and K-ras function may contribute to the clinical aggressiveness of pancreas cancer. Microsatellite instability and DNA mismatch repair defects may represent new mutator phenotype for pancreas carcinogenesis. Mutation of cell cycle regulators, such as inhibitor of CDK4 or p16 tumor suppressor gene, is a new molecular event in pancreas cancer. Mutation of cyclin-dependent kinases also may be involved in pancreas carcinogenesis. Loss or mutation of a new candidate tumor suppressor, DPC4 (deleted in pancreas carcinoma locus 4), is reported in pancreas cancer. The protein products of these gene mutations are potential tumor antigens, thus genotype expression can be detected by phenotype. Most of these emerging molecular genetic biomarkers are associated with regulation of cell growth and recognition, as well as gene expression, and may offer new insight into the cellular precursors to and genesis of pancreas cancer.
Chu
T M
TM
Department of Diagnostic Immunology Research and Biochemistry, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
D014408:Biomarkers, Tumor / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002455:Cell Division; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D004260:DNA Repair / Q000235:genetics; D004791:Enzyme Inhibitors / Q000378:metabolism; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D018895:Microsatellite Repeats; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics*
D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004791:Enzyme Inhibitors; D018844:Cyclin-Dependent Kinases