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阿曼弥漫性大B细胞淋巴瘤小队列中的p53突变/缺失谱

The p53 Mutation/Deletion Profile in a Small Cohort of the Omani Population with Diffuse Large B-Cell Lymphoma.

作者信息

Tamimi Yahya, Al-Harthy Sheikha, Al-Haddabi Ibrahim, Al-Kindi Mohammed, Babiker Hamza, Al-Moundhri Mansour, Burney Ikram

机构信息

Departments of Biochemistry, College of Medicine & Health Sciences, Sultan Qaboos University;

Departments of Pathology, Sultan Qaboos University Hospital, Muscat, Oman.

出版信息

Sultan Qaboos Univ Med J. 2014 Feb;14(1):e50-8. doi: 10.12816/0003336. Epub 2014 Jan 27.

Abstract

OBJECTIVES

Mutations/deletions affecting the TP53 gene are considered an independent marker predicting a poor prognosis for patients with diffuse large B-cell lymphoma (DLBCL). A cohort within a genetically isolated population was investigated for p53 mutation/deletion status.

METHODS

Deoxyribonucleic acid (DNA) samples were extracted from 23 paraffin-embedded blocks obtained from DLBCL patients, and subjected to polymerase chain reaction (PCR) amplification and sequencing of exons 4-9 of the p53 gene.

RESULTS

While 35% of patients analysed displayed allelic deletions (P <0.01), immunohistochemical analysis revealed a mutation rate of 69.5%. It is noteworthy that the rate of p53 mutations/deletions in this small cohort was found to be higher than that previously reported in the literature. Interestingly, patients with p53 mutations displayed a better overall survival when compared to those without. The survival of patients treated with rituximab-containing combination chemotherapy was significantly better than those who did not receive rituximab (P <0.05). Furthermore, a modelling analysis of the deleted form of p53 revealed a huge structural change affecting the DNA-binding domain.

CONCLUSION

The TP53 mutation/deletion status plays a role in mechanism(s) ruling the pathogenesis of DLBCL and may be useful for stratifying patients into distinct prognostic subsets.

摘要

目的

影响TP53基因的突变/缺失被认为是弥漫性大B细胞淋巴瘤(DLBCL)患者预后不良的独立标志物。对一个基因隔离人群中的队列进行了p53突变/缺失状态的研究。

方法

从23例DLBCL患者的石蜡包埋组织块中提取脱氧核糖核酸(DNA)样本,并对p53基因的第4至9外显子进行聚合酶链反应(PCR)扩增和测序。

结果

虽然35%的分析患者显示等位基因缺失(P<0.01),但免疫组化分析显示突变率为69.5%。值得注意的是,该小队列中的p53突变/缺失率高于先前文献报道的水平。有趣的是,与无p53突变的患者相比,有p53突变的患者总生存期更好。接受含利妥昔单抗联合化疗的患者生存率明显高于未接受利妥昔单抗的患者(P<0.05)。此外,对p53缺失形式的建模分析显示,其DNA结合结构域发生了巨大的结构变化。

结论

TP53突变/缺失状态在DLBCL发病机制中起作用,可能有助于将患者分层为不同的预后亚组。

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