Loss of heterozygosity in the tuberous sclerosis gene associated regions in adenocarcinoma of the lung accompanied by multiple atypical adenomatous hyperplasia
Loss of heterozygosity in the tuberous sclerosis gene associated regions in adenocarcinoma of the lung accompanied by multiple atypical adenomatous hyperplasia
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DOI：
10.1002/(sici)1097-0215(19980821)79:4
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发表时间：
1998-08-21
影响因子：
6.4
通讯作者：
Esumi, H
中科院分区：
文献类型：
--
作者：
Suzuki, K;Ogura, T;Esumi, H
为了研究人类肺癌中位于9号染色体长臂（9q）和16号染色体短臂（16p）的结节性硬化症复合物（TSC）相关区域的肿瘤抑制基因位点的潜在等位基因缺失，我们用染色体上的11个多态性标记分析了21对正常和肿瘤DNA。所有肿瘤均为肺腺癌，其中包括9例伴有多发性非典型腺瘤样增生（AAH）的腺癌。采用了精确的显微切割技术，随后进行聚合酶链反应（PCR）扩增，以防止对杂合性缺失（LOH）的低估。21例腺癌中有12例（57%）在9q上显示LOH。21例腺癌中有5例（24%）在9q的所有有信息位点上显示LOH，而7例（33%）在9q34上显示部分LOH。在这21例中，有5例（24%）在D9S149和D9S150之间（TSC1所在位置）显示部分LOH。在TSC1相关区域存在部分LOH的腺癌中，相关AAH的发生率显著更高（p = 0.0048）。21例腺癌中有12例（57%）在16p上显示LOH。在16p上有和没有LOH的腺癌之间，临床病理特征没有显著差异。综合这些数据，在高分化腺癌（p = 0.086）和伴有AAH（p = 0.081）的病例中，更频繁地观察到在TSC1和/或TSC2相关位点的部分LOH。总之，我们的结果表明，TSC相关区域是肺腺癌中肿瘤抑制基因的新候选位点，尤其是当伴有多发性AAH时。《国际癌症杂志（肿瘤学前瞻）》1998年79卷384 - 389页。（C）1998年威利 - 利斯公司
To investigate the potential allelic loss of tumor suppressor gene loci in the tuberous sclerosis complex (TSC)-associated regions located on the long arm of chromosome 9 (9q) and on the short arm of chromosome 16 (16p) in human lung carcinoma, we analyzed 21 paired normal and tumor DNAs with II polymorphic markers on the chromosomes. All tumors were adenocarcinoma of the lung, which included 9 adenocarcinomas with associated multiple atypical adenomatous hyperplasia (AAH). A precise microdissection technique followed by polymerase chain reaction (PCR) amplification to prevent under-evaluation of loss of heterozygosity (LOH) was used. Twelve of the 21 (57%) adenocarcinomas displayed LOH on 9q. Five of the 21 adenocarcinomas (24%) showed LOH at all informative loci on 9q, whereas 7 (33%) demonstrated partial LOH on 9q34. Among these 21, 5 (24%) showed partial LOH between D9S149 and D9S150, where TSCI is located. The incidence of associated AAH was significantly higher in adenocarcinoma harboring a partial LOH in the TSCI-associated region (p = 0.0048). Twelve of the 21 (57%) adenocarcinomas displayed LOH on 16p. No significant differences in the clinico-pathological characteristics could be discerned between adenocarcinomas with and without LOH on 16p. When combining these data, a partial LOH at TSCI- and/or TSC2-associated loci was observed more frequently in cases with well-differentiated adenocarcinoma (p = 0.086) and associated AAH (p = 0.081). In conclusion, our results suggest that the TSC-associated regions are new candidate loci for tumor suppressor genes in lung adenocarcinoma, especially when it is accompanied by multiple AAH. Int. J. Cancer (Pred. Oncol.) 79:384-389, 1998. (C) 1998 Wiley-Liss, Inc.