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Tumor Necrosis Factor- Allelic Frequency and Chromosome 6 Allelic Imbalance in Patients with Colorectal Cancer¹

Departments of Laboratory Medicine and Pathology [R. H., S. N. T.] and Division of Biostatistics [S. M., D. J. S.], Mayo Clinic and Foundation, Rochester, Minnesota 55905

The human tumor necrosis factor (TNF) locus is located on chromosome 6p21.3 and contains at least five polymorphic microsatellites. In this study, we compared the allelic frequencies derived from 50 normal controls to 64 patients with colorectal cancer at one of these loci, TNF. No differences in allelic frequencies were observed between these two groups (P = 0.47). However, sequencing of the TNF PCR product revealed two populations of TNF alleles; alleles with the expected DNA sequence (i.e., the expected number of AC/GT repeats) and alleles that contained 8-bp deletions adjacent to the microsatellite repeat. In addition, we also examined paired normal and tumor DNA from the colorectal cancer group for microsatellite alterations at the TNF locus, including allelic loss of heterozygosity and microsatellite instability. Of the 64 tumors examined, 13 (20%) demonstrated microsatellite instability, and 14 (42%) of 33 informative cases demonstrated allelic imbalance. Analysis of 10 additional chromosome 6 loci for allelic loss showed that 23 (47%) of 49 informative cases exhibited allelic 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 marker on chromosome 6. Examination of tumors for the minimal region of deletion overlap suggests the presence of tumor suppressor genes on both 6p and 6q.

¹ This study was funded by American Cancer Society Grant EDT-3.

² To whom reprints should be addressed, at Laboratory Genetics, 970 Hilton, Mayo Clinic, 200 First Street S.W., Rochester, MN 55905.

Received 7/26/95. Accepted 10/31/95.

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