LOW-FREQUENCY AND LATE OCCURRENCE OF P53 AND DCC ABERRATIONS IN COLORECTAL TUMORS

Whilst p53 aberrations have been documented in numerous malignancies, reports of alterations to the deleted in colorectal cancer (dcc) gene are infrequent, and studies investigating the status of both genes in the same colon tumour are rare. In this study we have analysed a panel of 35 pairs of normal and neoplastic human colorectal tissues for abnormalities in these tumour-suppressor genes. In contrast to previous studies we have found only a low incidence of mutations and deletions. p53 point mutations were identified in 8/35 tumours (22%). All were G.C to A.T transitions, with 7/8 occurring at CpG dinucleotides. p53 allelic loss was detected in 4/11 informative cases (36%). Although not quite attaining statistical significance, p53 alteration correlated with the adenoma/carcinoma transition. Gross dcc alterations were identified by Southern blotting in 7/35 (20%) tumours. Microsatellite analysis using two markers, one within and one proximal to the dcc gene, detected a low frequency of deletion overall (41% informative cases). 18q/dcc aberrations were associated with the progression of early to late carcinoma, rather than with increasing adenoma size, as has been previously reported. Both p53 alterations and dcc deletions were detected at a higher frequency in distal tumours than in proximal malignancies. Two tumours exhibiting microsatellite instability in both markers were each of proximal origin.