Role of BAX mutations in mismatch repair-deficient colorectal carcinogenesis

BAX gene mutations occur in approximately 50% of RER+ colorectal cancers. T o determine the role of these mutations in tumour progression we analysed m ultiple different tumour sites from RER+ colorectal cancers for BAX mutatio ns. Sixty colorectal carcinomas were analysed for microsatellite instabilit y at loci BAT-26, L-myc, TGF beta RII, D13S160 and D2S123. Twelve out of 60 tumours (20%) were RER+, Forty-five different tumour sites from the 12 RER + carcinomas were analysed for BAX mutations at the [(G)8] tract in exon 3, Six out of 12 (50%) RER+ tumours showed BAX mutations, four of which showe d a homogenous pattern of such mutations detected in all tumour sites. In t he other two cases, BAX mutations were present in some but not all tumour s ites sampled from the same patient. In contrast, TGF beta RII mutations wer e found in 9/12 cases (75%) and in each of these were present in all the sa mpled sites. Two cases showed neither BAX nor TGF beta RII mutation. These data suggest that mutations in TGF beta RII may occur at a very early stage in tumour progression, perhaps in the founder clone. BAX mutations, howeve r, are clearly not necessary for formation of the founder clone and can occ ur for the first time later in tumour progression.