CONSISTENT CHROMOSOME-3P DELETION AND LOSS OF HETEROZYGOSITY IN RENAL-CELL CARCINOMA
CONSISTENT CHROMOSOME-3P DELETION AND LOSS OF HETEROZYGOSITY IN RENAL-CELL CARCINOMA
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DOI：
10.1073/pnas.85.5.1571
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发表时间：
1988-03-01
影响因子：
11.1
通讯作者：
SUMEGI, J
中科院分区：
文献类型：
--
作者：
KOVACS, G;ERLANDSSON, R;SUMEGI, J
本文对34例散发性非遗传性肾细胞癌患者的肾细胞癌和正常肾组织进行了检查。在21例细胞遗传学检查的肿瘤中，有18例（86%）在3p11.2-p13带远端染色体臂3p处可检测到异常，表现为缺失，并伴有来自另一条染色体或单体3的一个片段的非互易易位。限制性片段长度多态性分析显示，21例患者中有16例（76%）存在D1S1杂合性缺失。11例患者中2例（18%）缺失D3S2杂合性。3p11.2和3p13之间断点的可变性，以及缺少来自另一条染色体的一致易位片段，表明存在遗传丢失机制，而显性致癌基因的激活似乎不太可能。再加上先前在家族病例中发现的3p14.2区域的参与，这些发现表明rcc可能是由“隐性癌症基因”的缺失引起的，就像视网膜母细胞瘤和Wilms肿瘤一样。相关位点必须位于3号染色体短臂上D1S1位点的端粒侧。
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 an 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.