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参与口腔和喉鳞状细胞癌早期肿瘤发生的8号染色体短臂区域的定位

Localization of chromosome 8p regions involved in early tumorigenesis of oral and laryngeal squamous carcinoma.

作者信息

El-Naggar A K, Coombes M M, Batsakis J G, Hong W K, Goepfert H, Kagan J

机构信息

Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA.

出版信息

Oncogene. 1998 Jun 11;16(23):2983-7. doi: 10.1038/sj.onc.1201808.

Abstract

We analysed 30 primary invasive oral and laryngeal squamous carcinomas (SC), with concurrent dysplastic lesions, for genetic alterations at 15 microsatellite loci on the short arm of chromosome 8. Overall, loss of heterozygosity (LOH) was observed, in at least one informative locus, in 27% of the dysplastic lesions and in 67% of the invasive carcinomas. The highest frequency of allele losses in dysplasia (20% and 17%), and invasive carcinoma (40% and 48%) were detected in the same D8S298 and LPL-tet loci located on chromosomes 8p21 and 8p22 respectively. The minimal region with LOH was limited to 4.6 megaBases (mBs) at 8p22 and 7.1 mBs at 8p21. In addition, allelic losses in both dysplastic and corresponding invasive specimens were noted at the same loci in some tumors suggesting their emergence from a common preneoplastic clone. Allele losses correlated significantly with male gender, oral and laryngeal sites and high proliferative index. The data suggest that inactivation of tumor suppressor gene(s), within these loci, may constitute an early event in the evolution of oral and laryngeal SC.

摘要

我们分析了30例伴有发育异常病变的原发性侵袭性口腔和喉鳞状细胞癌(SC),检测了8号染色体短臂上15个微卫星位点的基因改变。总体而言,在至少一个信息位点观察到杂合性缺失(LOH),发育异常病变中为27%,侵袭性癌中为67%。发育异常(20%和17%)和侵袭性癌(40%和48%)中,等位基因缺失频率最高的分别是位于8号染色体p21和p22的D8S298和LPL - tet位点。杂合性缺失的最小区域在8p22限于4.6兆碱基(mBs),在8p21限于7.1 mBs。此外,在一些肿瘤的发育异常和相应侵袭性标本中,在相同位点都发现了等位基因缺失,提示它们起源于一个共同的癌前克隆。等位基因缺失与男性性别、口腔和喉部位以及高增殖指数显著相关。数据表明,这些位点内肿瘤抑制基因的失活可能是口腔和喉鳞状细胞癌发生发展过程中的早期事件。

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