Kovacs G, Erlandsson R, Boldog F, Ingvarsson S, Müller-Brechlin R, Klein G, Sümegi J
Laboratory of Cytogenetics, Hannover Medical School, Federal Republic of Germany.
Proc Natl Acad Sci U S A. 1988 Mar;85(5):1571-5. doi: 10.1073/pnas.85.5.1571.
Renal cell carcinoma (RCC) and normal kidney tissues have been examined from 34 patients with sporadic, nonhereditary RCC. Eighteen of the 21 cytogenetically examined tumors (86%) had a detectable anomaly of chromosome arm 3p distal to band 3p11.2-p13, manifested as a deletion, combined with the nonreciprocal translocation of a segment from another chromosome or monosomy 3. Restriction-fragment-length polymorphism analysis showed loss of D1S1 heterozygosity in 16 of the 21 cases (76%). D3S2 heterozygosity was lost in 2 of 11 cases (18%). The variability of the breakpoint between 3p11.2 and 3p13 and the absence of a consistently translocated segment from another chromosome suggests a genetic-loss mechanism, while the activation of a dominant oncogene appears less likely. Together with the previously demonstrated involvement of the 3p14.2 region in a familial case, these findings suggest that RCCs may arise by the deletion of a "recessive cancer gene," as do retinoblastoma and Wilms tumor. The relevant locus must be located on the telomeric side of the D1S1 locus on the short arm of chromosome 3.
对34例散发的、非遗传性肾细胞癌（RCC）患者的肾细胞癌组织和正常肾组织进行了检查。在21例经细胞遗传学检查的肿瘤中，有18例（86%）在3p11.2 - p13带远端的3号染色体臂存在可检测到的异常，表现为缺失，伴有来自另一条染色体的片段的非相互易位或3号染色体单体性。限制性片段长度多态性分析显示，21例中有16例（76%）存在D1S1杂合性缺失。11例中有2例（18%）出现D3S2杂合性缺失。3p11.2和3p13之间断点的变异性以及另一条染色体上始终没有易位片段表明存在一种基因缺失机制，而显性癌基因的激活似乎不太可能。连同之前在一个家族性病例中证明的3p14.2区域的参与，这些发现表明肾细胞癌可能像视网膜母细胞瘤和Wilms瘤一样，通过“隐性癌基因”的缺失而发生。相关基因座必须位于3号染色体短臂上D1S1基因座的端粒侧。
