Chromosomal changes in colorectal adenomas: relationship to gene mutations and potential for clinical utility

Amy Leslie, Arlene Stewart, David U Baty, Dorothy Mechan, Louise McGreavey, Gillian Smith, C Roland Wolf, Mark Sales, Norman R Pratt, Robert J C Steele, Francis A Carey

    Research output: Contribution to journalArticle

    24 Citations (Scopus)

    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.
    Original languageEnglish
    Pages (from-to)126-135
    Number of pages10
    JournalGenes, Chromosomes and Cancer
    Volume45
    Issue number2
    Early online date18 Oct 2005
    DOIs
    Publication statusPublished - Feb 2006

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