DOWN REGULATION OF FAS GENE-EXPRESSION IN COLON-CANCER IS NOT A RESULT OF ALLELIC LOSS OR GENE REARRANGEMENT

Expression of Fas, an apoptosis-inducing receptor, in colonic epitheli um is progressively reduced during malignant transformation. We have e xamined the human Fas gene for loss of heterozygosity (LOH) and gross rearrangements in colon tumours and matched normal mucosa. Polymerase chain reaction (PCR) primers were designed to span a DraI restriction fragment length polymorphic site in the gene. Heterozygosity was detec ted in normal DNA samples by PCR amplification of the polymorphic site and restriction enzyme digestion. Thirty-eight of 88 patients (43%) w ith colon carcinomas were informative for the assay, and LOH was detec ted in 6 of the 38 (16%) corresponding tumours. Tumours from three pat ients with LOH did not express detectable Fas mRNA, and Fas expression was reduced or absent in 7 of 11 tumours from informative patients wi thout LOH. Southern blotting of tumour DNA samples was used to detect rearrangement of the Fas gene, but no altered hybridization patterns w ere observed in 64 tumours analysed. These findings indicate that disr uption of the Fas gene is not primarily responsible for the loss of Fa s protein expression reported in colon cancer. We have also shown that loss of Fas gene transcription is common in these tumours, which may be due to epigenetic gene silencing.