鼻咽癌染色体1p末端结构异常及其临床意义的初步研究

背景鼻咽癌染色体1p末端结构异常与鼻咽癌发生发展及预后的相关性目前仍然不清楚.目的探讨鼻咽癌 (nasopharyngeal carcinoma, NPC)染色体 1p末端 (1pter)结构异常与鼻咽癌发生发展及患者部分临床特征的相关性.设计以诊断为依据,设立对照组的回顾性研究.地点和对象实验由中山医科大学肿瘤防治实验研究部收集完成,研究对象为中山医科大学肿瘤医院就诊或住院的未经治疗的65例鼻咽癌患者鼻咽活检组织标本.干预采用组织中淋巴细胞分离法获取较纯的肿瘤细胞,应用1号染色体短臂端粒相关探针 (TelVysion 1p)及端粒连锁微卫星位点 D1S243分别对65例 NPC活检组织进行间期荧光原位杂交 (fluorescent in situ hybridization,FISH )及杂合性缺失 (loss of heterozygosity, LOH)和微卫星体不稳定(microsatellite instability,MI)分析.主要观察指标 观察鼻咽癌染色体 1p末端的缺失、扩增及微卫星体不稳定等结构异常情况及其与临床特征的关系.结果65例 NPC活检组织中,间期 FISH显示 1pter结构异常的有 20例,其中扩增 7例,缺失8例,扩增缺失共有 5例,其中 44例有临床分期资料的标本中,临床早期的异常频率为50.0% (2/4),而中晚期则为 30.0% (12/40),两者比较差异无显著性意义 (χ2=0.0655,P >0.05); 31例 NPC活检组织端粒连锁微卫星位点 D1S243的PCR-LOH/MI分析显示鼻咽癌染色体 1pter结构异常的有 16例 , 其中 MI13例,纯合性缺失(homogeneous deletion,HD)2例, LOH1例.两种方法在检查 1pter结构异常方面呈正相关(χ 2=4.775,P< 0.05),相关系数 r=0.392.结论 鼻咽癌染色体 1pter结构存在异常, 表现为扩增、缺失与微卫星体不稳定,其涉及的基因可能在临床早期参与了NPC的发生发展过程.鉴定其中的目的基因对 NPC的早期预防、诊断及治疗有一定临床意义.

Structural abnormalities of chromosome 1p termination in nasopharyngeal carcinoma and its clinical implications

BACKGROUND:Correlations between the structural abnormalities of chromosome 1pter in nasopharyngeal carcinoma(NPC) and its tumorigenesis and clinical significance are still unclear. OBJECTIVE: To investigate the correlations between the structural abnormalities of chromosome 1pter in NPC and the tumorigenesis of NPC. DESIGN:A retrospective study was performed to the control group according to the diagnosis. SETTING and PARTICIPANTS: The experiment was collected and completed in Reaearch Department of Sun Yat-Sen Cancer Center.Biopsy specimens from the nasopharynx of 65 cases of pathologically confirmed primary NPC without any therapy in the Sun Yat-Sen Univrsity Cancer Center were collected between the year 1998 and 2000 to survey. INTERVENTION: After the purification of cancerous cells from NPC biopsies with many noncancerous lymphocytes, interphase fluorescent in situ hybridization(FISH) and PCR-LOH/MI analysis of the somatic alterations of chromosomes 1pter in 65 cases of NPC biopsies were performed by using 1pter-related probe, TelVysion 1p, and telomere-linked microsatellite polymorphism site, D1S243,respectively. MAIN TOUCOME MEASURES: The abnormalities such as chromosome deletion, amplification and microsatellite instabilities(MI) and their clinical implications were examined and investigated. RESULTS:The somatic alterations of chromosome 1pter of NPC were detected in 20 of 65 cases with NPC, 8 of which showed allelic deletion,7 amplification and 5 both simultaneously.In available 44 patients with clinical stages, 2 of the 4 NPC cases in the early clinical stage were proved to be aberrations in chromosome 1pter, whereas 30.0% (12/40) of NPC patients in advanced clinical stage showed somatic structural aberrations of chromosome 1pter(χ 2=0.0655,P >0.05).PCR-LOH/MI analysis indicated that, out of the matched 31 NPC biopsies,16 had detectable aberrations, including 13 microsatellite instability(MI),2 homozygous deletion(HD) and 1 loss of heterozygosity(LOH). The two methods above were positively correlative significantly(χ 2=4.775,P< 0.05,r=0.392). CONCLUSION: There are frequent abnormalities of chromosome 1pter in primary NPC such as deletion, amplification and MI, suggesting that the genes in this region may be involved in the tumorigenesis of NPC.