Molecular changes in the Ki-ras and APC genes in colorectal adenomas and carcinomas arising in the same patient

The purpose of this study was to compare the molecular genetic changes in t he Ki-ras and adenomatous polyposis coli (APC) genes between adenomas and c arcinomas removed from the same patients. This comparison of benign and mal ignant tissue mould enhance understanding of the progression of molecular c hanges during the development of colorectal malignancy and similarities bet ween paired lesions could be indicative of a common aetiology. The basic pr ocedures used were DNA extraction from wax blocks of removed tissue, follow ed by polymerase chain reaction (PCR) and gel electrophoresis for mutations in the Ki-ras gene using single strand conformational polymorphism (SSCP); amplification of a CA repeat marker was used to assess for loss Of heteroz ygosity (LOH) of the APC gene, The main findings in 100 adenoma and carcino ma pairs for the Ki-ras gene were as follows: the frequency of Ki-ras mutat ion in the adenomas increased with increasing villous component, but did no t vary in the paired carcinomas; the frequency of Iii-rns mutation in, vill ous adenomas was greater than in carcinomas; and when both paired lesions h ad Ki-ras mutations, only 44% had the identical mutation. For the APC gene, the incidence of LOH in the adenomas did not var! by histological type; th e LOH status of the adenoma was associated with that of the paired carcinom a; but when both paired lesions had LOH of the APC gene, only 50% had LOH f or the same allele, In conclusion, these data on paired adenomas and carcin omas suggest that a Ki-ras mutation is not a consistent finding between the adenoma and carcinoma from the same bowel. The development of LOH of the A PC gene is a slightly more consistent finding between the pair, but is not always allelic-specific. Copyright (C) 2000 John Wiley & Sons, Ltd.