摘要目的 探讨MUS81基因突变和表达与喉癌发生发展的相关性.方法 应用聚合酶链反应-单链构象多态性分析技术结合DNA测序检测分析了42例喉癌患者MUS81基因第9、10外显子的突变;应用半定量逆转录-PCR和Western印迹方法分析MUS81基因在喉癌组织中的表达情况.结果 42例喉癌、癌旁组织标本中,癌旁正常组织均无突变,喉癌组织标本中19例发生突变,占45.2%(19/42),11例喉癌组织第9外显子发现有突变,占26.2%(11/42),8 例喉癌组织第10外显子有突变,占19%(8/42),分析表明具有统计学意义(P<0.01).逆转录-PCR结果表明,42例喉癌中有17例MUS81基因mRNA低表达,占40.48%(17/42).Western印迹方法分析结果表明,42例喉癌中有17例MUS81蛋白质低表达,占40.48%(17/42),经统计学分析肿瘤组与对照组差异有统计学意义(P<0.01).分析表明MUS81基因突变与mRNA和蛋白质低表达有显著相关性(P<0.01).统计结果显示喉癌MUS81基因突变与TNM分期、年龄和淋巴结转移无相关性(P>0.05).MUS81基因低表达与TNM分期、年龄和淋巴结转移无相关性(P>0.05).结论 发现MUS81基因在喉癌组织中有突变发生及表达异常,提示MU81基因突变和表达异常可能是喉癌发生及发展的重要因素之一.

abstractsObjective To investigate the association of mutations and expression of MUS81 gene with the tumorigenesis and progression of laryngeal squamous cell carcinoma (LSCC). Methods PCR-SSCP and DNA sequencing were carried out to examine mutations at exons 9 and 10 of MUS81 gene in 42 LSCC samples, with paired adjacent normal laryngeal tissues (PANLs) as control. Senti-quantitative RT-PCR and Western blot were used to detect the expression of MUS81 gene in the specimens. Results No mutation was detected in the control group. Among the 42 LSCC specimens, nineteen (45.2%) were found to harbor mutations, including 11 (26.2%) occurring within exon 9, and 8(19 % ) within exon 10. Seventeen(40.48 % ) samples showed lower mRNA level of the MUS81 gene ( P <0.01 ), and same proportion of samples had lower protein level ( P <0.01 ), suggesting that MUS81 gene was similarly down-regulated at both mRNA and protein levels in the LSCC samples. Furthermore, mutations of MUS81 gene did not significantly correlate with TNM stages, age and lymphoid node metastasis (P >0.05). Nor did the expression of MUS81 gene with the TNM stages, age and lymphoid node metastasis in LSCC ( P >0.05). Conclusion Mutations and abnormal expression of MUS81 gene in the LSCC tissues were observed, which suggested that abnormalities of MUS81 gene may play an important role in the tumorigenesis of LSCC.