title: Chromosomal changes in colorectal adenomas: relationship to gene mutations and potential for clinical utility.
abstract: Although the occurrence of both chromosomal aberrations and specific gene mutations in colorectal tumorigenesis is firmly established, the relationship between these different forms of genetic abnormality remains poorly understood. We have previously demonstrated, in colorectal adenocarcinomas, that mutations of APC, KRAS, and TP53 are each specifically associated with certain chromosomal aberrations. Using comparative genomic hybridization and mutational analysis of APC, KRAS, and TP53 to evaluate 78 colorectal adenomas, we have shown that several of the significant relationships between gene mutations and chromosomal abnormalities reported in colorectal adenocarcinomas also exist at the adenomatous stage. KRAS mutation correlated with 12p gain (P < 0.001) and TP53 mutation with both 20q gain and 18q loss (P = 0.03 for both). In addition, we have identified two chromosomal aberrations, gain of 13q and loss of 11q, that correlate with the presence of synchronous adenomas (P = 0.049 and P = 0.03, respectively) and several chromosomal changes (20p+, 20q+, 17p-, and 18q-) that are related to the onset of high-grade dysplasia. These data strengthen our previous contention that the co-occurrence of specific gene mutations and chromosomal changes is not random and significant relationships do exist. Our findings also raise the possibility that certain chromosomal aberrations may act as important clinical biomarkers.
authors.affiliation: Department of Surgery & Molecular Oncology, University of Dundee, Ninewells Hospital, United Kingdom. amy.leslie@tuht.scot.nhs.uk
authors.forename: Amy
authors.initials: A
authors.lastname: Leslie
authors.forename: Arlene
authors.initials: A
authors.lastname: Stewart
authors.forename: David U
authors.initials: DU
authors.lastname: Baty
authors.forename: Dorothy
authors.initials: D
authors.lastname: Mechan
authors.forename: Louise
authors.initials: L
authors.lastname: McGreavey
authors.forename: Gillian
authors.initials: G
authors.lastname: Smith
authors.forename: C Roland
authors.initials: CR
authors.lastname: Wolf
authors.forename: Mark
authors.initials: M
authors.lastname: Sales
authors.forename: Norman R
authors.initials: NR
authors.lastname: Pratt
authors.forename: Robert J C
authors.initials: RJ
authors.lastname: Steele
authors.forename: Francis A
authors.initials: FA
authors.lastname: Carey
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D002869:Chromosome Aberrations; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D017931:DNA Primers; D005260:Female; D017491:Genes, APC; D011905:Genes, ras; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D009154:Mutation; D009693:Nucleic Acid Hybridization; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D017931:DNA Primers; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53