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人类口腔癌中13号染色体长臂14.3区域的等位基因缺失:与淋巴结转移的相关性

Allelic loss of chromosome 13q14.3 in human oral cancer: correlation with lymph node metastasis.

作者信息

Ogawara K, Miyakawa A, Shiba M, Uzawa K, Watanabe T, Wang X L, Sato T, Kubosawa H, Kondo Y, Tanzawa H

机构信息

Department of Oral Surgery, School of Medicine, University of Chiba, Japan.

出版信息

Int J Cancer. 1998 Aug 21;79(4):312-7. doi: 10.1002/(sici)1097-0215(19980821)79:4<312::aid-ijc2>3.0.co;2-y.

Abstract

To evaluate the role of chromosome 13 deletions in oral squamous cell carcinoma (SCC) progression and to define the precise localization of putative tumor suppressor genes, we studied tumors from 34 unrelated patients with oral SCC by the polymerase chain reaction (PCR)-loss of heterozygosity (LOH) assay, using 18 different polymorphic loci. Chromosome 13q allelic losses (LOH) were observed in 67.6% at 1 or more loci. These results enabled the identification of a putative minimal region of deletion mapped at 13q14.3. The commonly deleted region is located close, but telomeric to the RB1 locus. We also examined the same samples for inactivation of the RB1 gene by immunohistochemical analysis of paraffin-embedded samples, but no significant variation in RB protein expression was detected. In addition, we also performed PCR-single-strand conformational polymorphism (SSCP) analysis to detect any mutation of the RB1 gene using 52 primer pairs, which covers all exons of this gene. We found no mutations of the RB1 gene in our samples. Interestingly, we found significant correlation between LOH of 13q14.3 and lymph node metastasis. Our results indicate that LOH of 13q is a common event in oncogenesis and/or progression of oral SCC, and also suggest the existence of a new suppressor gene near D13S273-D13S176 loci which may play a role in these events.

摘要

为评估13号染色体缺失在口腔鳞状细胞癌(SCC)进展中的作用,并确定假定肿瘤抑制基因的精确定位,我们使用18个不同的多态性位点,通过聚合酶链反应(PCR)杂合性缺失(LOH)分析,研究了34例无关口腔SCC患者的肿瘤。在1个或更多位点观察到13q等位基因缺失(LOH)的比例为67.6%。这些结果使得能够确定一个假定的最小缺失区域定位于13q14.3。常见的缺失区域位于靠近RB1基因座但在其端粒侧。我们还通过对石蜡包埋样本进行免疫组织化学分析,检测了相同样本中RB1基因的失活情况,但未检测到RB蛋白表达的显著差异。此外,我们还使用覆盖该基因所有外显子的52对引物进行PCR单链构象多态性(SSCP)分析,以检测RB1基因的任何突变。我们在样本中未发现RB1基因的突变。有趣的是,我们发现13q14.3的LOH与淋巴结转移之间存在显著相关性。我们的结果表明,13q的LOH是口腔SCC发生和/或进展中的常见事件,也提示在D13S273 - D13S176位点附近存在一个新的抑制基因可能在这些事件中起作用。

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