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

目的探讨Werner综合征相关基因（WRN）在普通人群骨、软组织肿瘤和甲状腺癌中的作用，我们检测了杂合突变的频率，（种系突变）在基因位点使用非-肿瘤组织取自55名骨和软组织肿瘤患者和68名甲状腺癌患者。这很有趣，因为有一些报告坚持认为，ATM基因位点杂合突变可显著增加乳腺癌死亡率，本研究采用的材料主要为外周血和部分石蜡包埋组织，分析方法为突变等位基因特异性扩增，其中突变型4（Mut 4）分别见于骨和软组织肿瘤和甲状腺癌，前者是28岁的男性，上臂有神经纤维瘤，后者是45岁的女性，乳头状癌，滤泡型。由于Mut 4解释了大约50%的所有Werner综合征相关突变，总体突变率估计为1/31，与估计值相比，（1/200至1/500），其源自Werner综合征（一种常染色体隐性遗传疾病）的发病率，1/500，000至1/1，000，000。提示WRN基因在普通人群骨和软组织肿瘤及甲状腺癌的发生中起重要作用。

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.