p53 mutations in mantle cell lymphoma are associated with variant cytology and predict a poor prognosis
p53 mutations in mantle cell lymphoma are associated with variant cytology and predict a poor prognosis
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DOI：
10.1182/blood.v87.10.4302.bloodjournal87104302
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发表时间：
1996-05-15
期刊：
影响因子：
20.3
通讯作者：
Weisenburger, DD
中科院分区：
文献类型：
--
作者：
Greiner, TC;Moynihan, MJ;Weisenburger, DD
p53抑癌基因突变已被描述在几个亚型的非霍奇金淋巴瘤，但发生率p53突变套细胞淋巴瘤（MCL）是未知的。我们假设，与典型的MCL相比，具有变异或高级别细胞学的MCL病例具有更高的p53突变可能性。我们还对MCL中p53突变的预后意义感兴趣。因此，一系列的53个良好的特征性病例的MCL与DNA从62个组织样本进行了分析的聚合酶链反应与变性梯度凝胶电泳的外显子5-8的p53。免疫过氧化物酶的研究与抗体DO-7的p53蛋白也进行了冷冻切片。我们在53例MCL中发现了8例（15%）p53基因突变。错义突变占主导地位，50%的突变发生在已知的p53热点密码子。在21例变异细胞学（即间变性或母细胞性）病例中，6例（28.6%）有p53突变，而32例典型MCL细胞学病例中仅2例（6.3%）有p53突变（P = 0.05），2例患者p53突变先于变异细胞学的发展。p53蛋白在8例p53突变中有6例（75%）过度表达，而在45例野生型病例中无一例过度表达。突变型p53病例的中位生存期仅为1.3年（全部死亡），而生殖系p53病例的中位生存期为5.1年（P = 0.023）。这些结果表明，p53突变可能是一种机制，参与发展的变异形式的MCL，并表明，p53突变的MCL预测预后不良。(C)1996年，美国血液学会。
Mutations of the p53 tumor suppressor gene have been described in several subtypes of non-Hodgkin's lymphoma, but the incidence of p53 mutations in mantle cell lymphoma (MCL) is unknown. We hypothesized that cases of MCL with a variant or high-grade cytology would have a higher likelihood of p53 mutations than typical MCL. We were also interested in the prognostic significance of p53 mutations in MCL. Therefore, a series of 53 well-characterized cases of MCL with DNA from 62 tissue samples was analyzed by the polymerase chain reaction with denaturing gradient gel electrophoresis for exons 5-8 of p53. Immunoperoxidase studies with the antibody DO-7 to p53 protein were also performed on frozen sections. We found mutations of the p53 gene in 8 of the 53 cases (15%) of MCL. Missense mutations predominated, and 50% of the mutations occurred at known p53 hotspot codons. Of 21 cases with variant cytology (ie, anaplastic or blastic), 6 (28.6%) had p53 mutations as compared with only 2 of 32 cases (6.3%) with typical MCL cytology (P = .05), and p53 mutations preceded the development of variant cytology in 2 patients. Overexpression of p53 protein was observed in 6 of the 8 cases (75%) with p53 mutations and in none of the 45 wild type cases. The median survival of the cases with mutant p53 was only 1.3 years (all died), whereas the median survival of cases with germline p53 was 5.1 years (P = .023). These results suggest that mutations of p53 may be one mechanism involved in the development of variant forms of MCL and indicate that p53 mutations in MCL predict a poor prognosis. (C) 1996 by The American Society of Hematology.