TUMOR-NECROSIS-FACTOR-ALPHA ALLELIC FREQUENCY AND CHROMOSOME-6 ALLELIC IMBALANCE PATIENTS WITH COLORECTAL-CANCER

The human tumor necrosis factor (TNF) locus is located on chromosome 6 p21.3 and contains at least five polymorphic microsatellites. In this study, we compared the allelic frequencies derived from 50 normal cont rols to 64 patients with colorectal cancer at one of these loci, TNF a lpha. No differences in allelic frequencies were observed between thes e two groups (P = 0.47). However, sequencing of the TNF alpha PCR prod uct revealed two populations of TNF alpha alleles; alleles with the ex pected DNA sequence (i.e., the expected number of AC/GT repeats) and a lleles that contained 8-bp deletions adjacent to the microsatellite re peat. In addition, we also examined paired normal and tumor DNA from t he colorectal cancer group for microsatellite alterations at the TNF a lpha locus, including allelic loss of heterozygosity and microsatellit e instability. Of the 64 tumors examined, 13 (20%) demonstrated micros atellite instability, and 14 (42%) of 33 informative cases demonstrate d allelic imbalance. Analysis of 10 additional chromosome 6 loci for a llelic loss showed that 23 (47%) of 49 informative cases exhibited all elic imbalance with at least one chromosome 6p marker, 23 (47%) of 49 with at least one 6q marker, and 29 (59%) of 49 with at least one mark er on chromosome 6. Examination of tumors for the minimal region of de letion overlap suggests the presence of tumor suppressor genes on both 6p and 6q.