Frequent allelic losses on the short arm of chromosome 1 and decreased expression of the p73 gene at 1p36.3 in squamous cell carcinoma of the oral cavity.
Frequent allelic losses on the short arm of chromosome 1 and decreased expression of the p73 gene at 1p36.3 in squamous cell carcinoma of the oral cavity.
复制标题
口腔鳞状细胞癌中 1 号染色体短臂上频繁的等位基因丢失以及 1p36.3 处 p73 基因的表达降低。
DOI：
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发表时间：
2002
影响因子：
5.2
通讯作者：
H. Tanzawa
中科院分区：
文献类型：
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作者：
D. Araki;K. Uzawa;Toshihide Watanabe;M. Shiiba;A. Miyakawa;H. Yokoe;H. Tanzawa
1号染色体(1p)短臂上的杂合性缺失(LOH)在一系列人类恶性肿瘤中已有报道。为了研究抑癌基因的可能存在，我们利用位于1p的15个多态微卫星标记检测了41例口腔鳞状细胞癌(OSCC)的杂合性缺失。在分析的至少一个基因座有信息的41个病例中，有30个(73%)观察到杂合性缺失。发现了两个不同的常见等位基因缺失区域：D1S243的远端区域(1p36.3)和D1S160的近端区域(1p36.1)。此外，还对位于1p36.3的候选抑癌基因p73的可能参与情况进行了评估。聚合酶链式反应-单链构象多态(PCR-SSCP)分析显示，所有分析样本(n=41)均未发现该基因突变。另一方面，半定量逆转录-聚合酶链式反应(RT-PCR)显示，25%的原发肿瘤(n=20)p73基因表达缺失或降低。所有p73基因表达下调的病例临床分类为IV期，但在同一样本中未检测到该基因位点的杂合性缺失。此外，DNA脱甲基剂5-氮-2‘-脱氧胞苷处理口腔鳞癌细胞系后，p73基因的mRNA再次表达，并下调该基因的表达。这些发现表明，在1p31.1和1p31.3上可能存在至少两个不同的肿瘤抑制基因因等位基因缺失而失活。此外，p73基因可通过甲基化依赖的沉默而失活，并与口腔鳞癌的肿瘤进展有关。
Frequent loss of heterozygosity (LOH) on the short arm of chromosome 1 (1p) has been reported in a series of human malignancies. To investigate the possible existence of tumor suppressor locus (or loci), we examined 41 primary oral squamous cell carcinomas (OSCCs) for LOH using a panel of 15 polymorphic microsatellite markers located on 1p. LOH was observed in 30 of 41 cases (73%) that were informative for at least one of the loci analyzed. Two distinct regions of common allelic loss were identified: a distal region at D1S243 (1p36.3), and proximal region at D1S160 (1p36.1). In addition, the possible involvement of the p73, a candidate tumor suppressor gene located on 1p36.3, was also evaluated. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis revealed no mutation of the gene in all samples analyzed (n=41). On the other hand, semi-quantitative reverse transcription-PCR (RT-PCR) demonstrated that 25% of primary tumors (n=20) had absent or reduced mRNA expression of the p73 gene. All cases showing down-regulation of the p73 gene were clinically classified as stage IV, but we could not detect any LOH at the gene locus in the same samples. Furthermore, re-expression of the p73 gene mRNA was induced in OSCC-derived cell lines showing down-regulation of the gene expression after treatment with 5-aza-2'-deoxycytidine, a DNA demethylating agent. These findings suggest that there may be at least two distinct tumor suppressor genes inactivated by allelic deletion on 1p31.1 and 1p31.3, respectively. In addition, the p73 gene could be inactivated by the methylation-dependent silencing of this gene, and associated with the tumor progression of human OSCC.