Tumor development mechanism and its risk evaluation in Werner syndrome

沃纳综合症是研究衰老和癌症的一个有趣的模型。到目前为止，我们发现甲状腺癌、骨肉瘤、软组织肉瘤、髓系疾病/MDS、脑膜瘤和黑色素瘤6种罕见肿瘤在Werner综合征中增加，而在一般人群中常见的肿瘤没有增加。在本研究中，我们研究了(1)WRN解旋酶缺陷与肿瘤发生的关系，(2)Werner综合征的肿瘤风险评估。关于第一个问题，我们收集了7例肺恶性肿瘤，因为在肺肿瘤中，肿瘤病因与组织学/遗传改变的关系已经比较明确。在第二期中，我们从相关机构和研究合作者或通过PubMed和Igaku-Chuo-Zasshi等公共数据库收集了133例非上皮性肿瘤（包括110例恶性肿瘤）和75例上皮性肿瘤的数据和/或材料。因此，我们更新了肿瘤档案，提供了新的肿瘤谱：软组织肉瘤（含皮下）37例，黑色素瘤34例，白血病/MDS 23例，脑膜瘤21例，骨肉瘤14例，脑肿瘤4例，甲状腺癌28例，皮肤癌10例，肝癌7例，乳腺癌6例，胃癌6例，肺癌5例，结肠癌1例，无前列腺癌。与1996年公布的统计数字相比，除黑色素瘤外，软部肉瘤和皮肤癌的人数有所增加。特别有趣的是，我们现在有多达39个与皮肤有关的恶性肿瘤，包括皮下肿瘤。其中黑色素瘤23例，基底细胞癌5例，鳞状细胞癌3例，皮脂腺癌1例，鲍文氏病1例，恶性肿瘤1例，皮肤良性肿瘤太阳角化病1例，新细胞痣1例，皮下肉瘤2例，恶性纤维组织瘤2例，急性T细胞白血病1例。

Werner syndrome is an interesting model for researches both of aging and cancer. We have so far revealed that six kinds of rare tumors, i.e. thyroid carcinoma, bone sarcoma, soft part sarcoma, myeloid disorders/MDS, meningioma and melanoma, were increased and that tumors common in general populations were not increased in Werner syndrome.In the current study, we have investigated (1) relationships between WRN helicase deficit and tumorigenesis and (2) evaluation of tumor risk in Werner syndrome.Regarding the first issue, for further analysis in the future, we collected seven cases of lung malignant tumors because relations between tumor causes and histology/genetic changes were relatively well established in lung tumors.For the second issue, we gathered data and/or materials of 133 non-epithelial (including 110 malignant) and 75 epithelial tumors from our related institutions and research collaborators or through examining public data bases such as the PubMed and the Igaku-Chuo-Zasshi. As a result, we updated our tumor files, providing the new tumor spectrum : 37 soft part sarcoma (including subcutaneous ones), 34 melanomas, 23 leukemia/MDS, 21 meningiomas, 14 bone sarcomas, 4 brain tumors as well as 28 thyroid carcinomas, 10 skin carcinomas, 7 liver carcinomas, 6 breast carcinomas, 6 gastric carcinomas, 5 lung carcinomas, 1 colonic carcinoma and no prostatic carcinoma. As compared with the previous statistics published in 1996, increased soft part sarcoma and skin cancers other than melanoma were noted. Particularly, it was interesting that we had now as many as 39 malignant tumors related to skin, including subcutaneous ones. Details were 23 melanomas, 5 basal cell carcinomas, 3 squamous cell carcinomas, 1 sebaceous gland carcinoma, 1 Bowen's disease, and 1 carcinoma NOS. Benign skin tumors were 1 solar keratosis, 1 nevocellular nevus, and subcutaneous sarcomas included 2 malignant fbrous histioctomas and 1 acute T cell leukemia.