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

医学 突变 美罗华 淋巴瘤 外显子 弥漫性大B细胞淋巴瘤 癌症研究 聚合酶链反应 人口 免疫组织化学 基因 肿瘤科 病理 内科学 生物 遗传学 环境卫生
作者
Yahya Tamimi,Sheikha Al-Harthy,Ibrahim Al-Haddabi,Mohammed Nasser Al-Kindi,Hamza A. Babiker,Mansour Al-Moundhri,Ikram Burney
出处
期刊:Sultan Qaboos University Medical Journal [Sultan Qaboos University]
卷期号:14 (1): 50-58 被引量:4
标识
DOI:10.12816/0003336
摘要

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.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.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.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.

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