T细胞淋巴瘤p53突变与其周围微卫星改变的研究

p53 mutation and microsatellite alteration in T cell lymphoma:38 cases

目的探讨T细胞淋巴瘤p53突变和其周围微卫星DNA的改变及两者的关系，以进一步研究T细胞淋巴瘤的分子遗传学发病机制。方法采用PCR、PCR-SSCP技术观察38例T细胞淋巴瘤的肿瘤组织及其肿瘤旁淋巴组织或同一病例的反应性增生淋巴结组织进行p53基因外显子5-8的点突变研究和p53周围4个微卫星位点D17S945、D17S938、D17S947、D17S926的微卫星（microsatellite，MS）改变：微卫星不稳定性（microsatellite instability，MSI）和杂合性缺失（loss of heterozygosity，LOH）分析。结果p53基因外显子5-8总突变率为39．47％（15／38）。微卫星改变的阳性率为23．68％（9／38），LOH为7．89％（3／38）。各位点MSI、LOH频率介于2．86％-18．42％和0-5．26％。微卫星改变阳性肿瘤的p53突变率为55．56％（5／9），阴性者为34．48％（10／29）（P〉0．05）。D17S926和D17S947位点LOH阳性组与阴性组的p53突变率分别为100％、36．11％（P〉0．05）。结论T细胞淋巴瘤中存在微卫星改变和p53基因突变，两者发生无明显关系。但微卫星改变阳性的肿瘤，p53突变倾向于高发。

Objective To determine the mutations of exons 5,6, 7 and 8 of p53 gene and the alteration of microsatellite DNA around it, and investigate their relationship in T-cell lymphoma. Methods We measured frequencies of p53 gene point mutation in exons 5 to 8 by PCR-SSCP methods and detected microsatellite alteration （MA） including microsatellite instability （MSI） and loss of heterozygosity （LOH） by PCR-based methods at 4 microsatellite loci （D17S945, D17S938, D17S947 and D17S926） around p53 gene in tumor mass and adjacent normal lymphatic tissue or reactive hyperplasia lymph node excised from 38 cases of T-cell lymphoma. Results The frequency of p53 gene mutation, MA, and LOH was 39.47% （ 15/38 ）, 23.68% （9/38）, and 7.89% （3/38）, respectively. At the 4 microsatellite loci, the frequency of MSI and LOH varied from 2. 86% to18.42% and from 0 to 5.26% , respectively. The mutation frequency of p53 gene in MA positive cases was 55.56% （5/9）, and in MA negative group was 34.48% （10/29）, but the difference was not significant（ P 〉 0.05 ）. Additionally, at D17S926 and D17S947, the mutation frequency of p53 gene in LOH positive cases was 100% and in the negative cases was 36.11% （ P 〉 0.05 ）. Conclusion There are MA and mutation of p53 gene in T-cell lymphoma though no significant correlation between them. But, MA positive cases might experience high mutation of 1353 gene in T-cell lymphoma.