title: Genomic instability occurs in colorectal carcinomas but not in adenomas.
abstract: Genomic instability, as demonstrated by the presence of additional alleles at short tandemly repeated (STR) loci, has recently been observed in colorectal tumours from individuals with hereditary nonpolyposis colorectal cancer (HNPCC), and in some sporadic tumours. These neoplasms have been called replication error positive (RER+). In this study, we confirm the presence of genomic instability in a proportion of unselected colorectal carcinomas but find no evidence of instability in adenomas. We further report replication errors in a tetranucleotide sequence, and in STRs within two tumour suppressor genes. 108 colorectal adenocarcinomas and 46 adenomas were analysed for the presence of variant bands at 4-15 microsatellite markers. Seven (6.5%) of carcinomas were RER+, four of which originated from the proximal colon. Analysis of the adenomas and of matched adenoma-carcinoma and carcinoma-metastatic samples from four patients suggests that the replication errors may occur during the development of carcinomas but are rare in adenomas.
authors.affiliation: Glaxo Gastroenterology Laboratory, Clinical Research Centre, Brisbane, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Young
authors.forename: B
authors.initials: B
authors.lastname: Leggett
authors.forename: C
authors.initials: C
authors.lastname: Gustafson
authors.forename: M
authors.initials: M
authors.lastname: Ward
authors.forename: J
authors.initials: J
authors.lastname: Searle
authors.forename: L
authors.initials: L
authors.lastname: Thomas
authors.forename: R
authors.initials: R
authors.lastname: Buttenshaw
authors.forename: G
authors.initials: G
authors.lastname: Chenevix-Trench
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000236:Adenoma / Q000235:genetics*; D002872:Chromosome Deletion; D015179:Colorectal Neoplasms / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D004261:DNA Replication / Q000235:genetics*; D016147:Genes, Tumor Suppressor / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D014407:Tumor Cells, Cultured