CANCER INCIDENCE IN GENERAL POPULATION WITH HETEROZYGOUS MUTATIONS AT THE GENE LOCUS RESPONSIBLE FOR WERNER SYNDROME.

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To investigate the role of Werner syndrome responsible gene (WRN) in bone and soft tissue tumors and thyroid cancers arising in general population, we examined the frequency of heterozygous mutations (germline mutations) at the gene locus using non-tumorous tissues taken from 55 bone and soft tissue tumor patients and 68 thyroid cancer patients.This is interesting because there are some reports which insist that in people who have heterozygous mutations in the ATM gene locus, breast cancer mortality is significantly increased.Materials used in this study were mostly peripheral blood and partly archival paraffin embedded tissues.Analytical methods were the mutant allele specific amplification.Among them, the mutation type 4 (Mut 4) was found one in bone and soft tissue tumors and one in thyroid cancers, the frequency of which was 1/62.The former was 28-year-old male with neurofibroma on his upper arm, and the latter was 45-year-old female with papillary carcinoma, follicular variant.Since the Mut 4 explains about 50 % of all Werner syndrome-related mutations, the overall mutation rate is estimated to be 1/31.This rate is extremely high as compared with an estimate (1/200 to 1/500) derived from the incidence of Werner syndrome, an autosomal recessive hereditary disease, 1/500,000 to 1/1,000,000.Consequently, the WRN gene is suggested to play an important part in the genesis of bone and soft tissue tumors and thyroid cancers among general population.