Frequent loss of heterozygosity in human primary squamous cell and colon carcinomas at 7q31.1: evidence for a broad range tumor suppressor gene.
Consistent deletions and loss of heterozygosity (LOH) in polymorphic markers in a determinate chromosomal fragment are known to be indicative of a closely mapping tumor suppressor gene. Deletion of the long arm of chromosome 7 is a frequent trait in many kinds of human primary tumors. We studied LOH of 14 markers on chromosome 7q in order to determine the location of a putative tumor suppressor gene in human primary squamous cell carcinoma of the head and neck and in human primary colon carcinomas. Samples were obtained from 18 primary squamous cell carcinomas of the head and neck and 18 primary colon carcinomas surgically removed from patients at the Fox Chase Cancer Center. Loss of heterozygosity was studied performing PCR amplifications of a set of 14 CA microsatellite repeats encompassing 7q21-qter. Of 18 squamous cell carcinomas of the head and neck cases studied, 12 had LOH at one or more loci on 7q. Fifty-three percent of 15 informative cases had LOH of the CA microsatellite dinucleotide repeat marker D7S522 at 7q31.1-7q31.2. Eleven of 18 colon carcinoma cases had LOH of one or more markers assayed, and the maximum LOH (80% of 10 informative cases) was at D7S522. Distributions of percentage of LOH in both tumor types were normally distributed around microsatellite D7S522. The high incidence of LOH in both tumor types studied suggests that a tumor suppressor gene relevant to the development of epithelial cancers is present on the 7q31.1-31.2, confirming our previous functional evidence for a tumor suppressor gene on chromosome 7.
Zenklusen
J C
JC
University of Texas, M. D. Anderson Cancer Center, Science Park-Research Division, Smithville 78957.
Thompson
J C
JC
Klein-Szanto
A J
AJ
Conti
C J
CJ
D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7; D003110:Colonic Neoplasms / Q000235:genetics*; D004276:DNA, Satellite / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D016133:Polymerase Chain Reaction
D004276:DNA, Satellite