title: There is no increase in frequency of somatic mutations in metastases compared with primary colorectal carcinomas with microsatellite instability.
abstract: This study investigates the molecular features of metastasis in sporadic colon carcinomas with high-level microsatellite instability (MSI-H). DNA from 51 regions from 10 MSI-H metastatic carcinomas and 26 corresponding metastases was analyzed for mutations in TGFBRII, IGFIIR, BAX, MSH3, MSH6, and TCF4, which are associated with MSI-H carcinomas. In addition, 10 metastatic and 10 non-metastatic MSI-H carcinomas and 10 metastatic microsatellite-stable (MSS) carcinomas were examined for expression of vascular endothelial growth factor (VEGF) and mutant TP53. The frequency of microsatellite instability and somatic mutations was not significantly increased in the metastases compared with the that of primary carcinomas. Although significantly fewer MSI-H carcinomas expressed VEGF (P < 0.01) and mutant TP53 (P < 0.005) than MSS carcinomas, there was no difference in VEGF and mutant TP53 expression in metastatic and non-metastatic MSI-H carcinomas. In conclusion, metastasis does not appear to be associated with an increase in somatic mutation rate in any of the genes examined in MSI-H colon carcinomas. Furthermore, VEGF and TP53 expression did not appear to be involved in metastasis in MSI-H colon carcinomas.
authors.affiliation: Department of Cancer Genetics, Kolling Institute, Royal North Shore Hospital, St. Leonards, NSW and University of Sydney, Sydney, Australia.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Barnetson
authors.forename: Robert
authors.initials: R
authors.lastname: Eckstein
authors.forename: Bruce
authors.initials: B
authors.lastname: Robinson
authors.forename: Margaret
authors.initials: M
authors.lastname: Schnitzler
mesh_terms: D015179:Colorectal Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000235:genetics; D016368:Frameshift Mutation; D005787:Gene Frequency / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D008113:Liver Neoplasms / Q000737:chemistry / Q000235:genetics / Q000556:secondary; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008222:Lymphokines / Q000096:biosynthesis / Q000235:genetics; D018895:Microsatellite Repeats / Q000235:genetics*; D009154:Mutation; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D009852:Omentum; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors