RB患者肿瘤及体细胞中Rb基因点突变谱及其特征和意义

目的：研究RB患者肿瘤及体细胞巾Rb基因点突变的频率，特征及其在肿瘤遗传易感性的传递及肿瘤形成机制中所起的作用。方法：SSCP分析及直接DNA序列分析。结果：在302例经Southern blotting杂交证实无明显Rb基因缺失或重排的RB患者的肿瘤或外周血白细胞DNA中共发现187个Rb基因点突变。结沦：Rb基因点突变几乎随机分布在整个编码区，常常导致氨基酸密码突变为终止密码，阅读框架移位或mRNA拼接异常，产生缩短丁的或缺乏某个外显子编码氨基酸的蛋白质。并以半个碱基取代占绝大多数。缺失或插入突变通常是一个或二个碱基的微小病变。（中华眼底病杂志，1995，11：240-243）

SPECTRUM AND CHARACTERIZATION OF RB GENE POINT MUTATONS INPRIMARY TUMORS AND SAMATIC CELLS OF PATIENTS WITH RETINOBLASTOMA

PURPOSE:To investigate the frequency and character of Rb gene point mutations in primary tumors and somatic cells of patients with retinoblastoma. METHODS:SSCP and PCR-associated direct sequencing.RESULTS: A total of 187 subtle mutations was found in 302 cases ofretinoblastoma patients.CONCLUSIONS: Rb point mutations randomly located in 128 sites of Rb gene,Among 187 mutations,129 mutations were single base substitutbms,57 mutations were microdeletions or microinsertions and one was C→GA,The majority of mutations either resulted in the direct creation a stop codon or frame shift or aberrant splicing. Only were 18 missense mutations found,In addition,about 63% of bilateral RB and 18% of unilateral RB showed germline Rb gene point mutations.（Chin J Ocul Fundus Dis,1995,11:240-243）