文章：

染色体17非整倍体、TP53基因缺失、表达及其rs1042522变异与多发性骨髓瘤风险及对沙利度胺/硼替佐米治疗反应的关联性研究

Association of Chromosome 17 Aneuploidy,TP53Deletion, Expression and Its rs1042522 Variant with Multiple Myeloma Risk and Response to Thalidomide/Bortezomib Treatment

原文发布日期：27 September 2023

DOI: 10.3390/cancers15194747

类型: Article

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英文摘要：

Multiple myeloma (MM) is a multifactorial genetic disorder caused by interactive effects of environmental and genetic factors. The properlocusof theTP53gene (17p13.1) and its protein is essential in genomic stability. The most common variant of theTP53gene—p.P72R (rs1042522)—shows functional variation. The aim of our study was a complex analysis of theTP53p.P72R variant andTP53gene expression in relation to chromosomal changes of theTP53genelocus, as well as MM risk and outcome. Genomic DNA from 129 newly diagnosed MM patients was analyzed by methods of automated DNA sequencing (forTP53variant analysis) and cIg-FISH (for chromosomal aberrations analysis). RNA was used in real-time PCR to determine theTP53expression. In MM patients, theTP53variant was not in Hardy–Weinberg equilibrium. The RR genotype was associated with lower MM risk (OR = 0.44,p= 0.004). A higher number of plasma cells was found in patients with RR genotype in comparison to those with PP + PR genotypes (36.74% vs. 28.30%,p= 0.02). A higher expression of theTP53gene was observed in PP + PR genotypes vs. RR homozygote (p< 0.001), in smokers vs. non-smokers (p= 0.02). A positive Pearson’s correlation was found between theTP53expression level and the number of plasma cells (r = 0.26,p= 0.04). The presence of chromosome 17 aberrations with or withoutTP53 locusdid not affect the MM risk and outcome. Similar results were observed in the case ofTP53gene expression and the p.P72R variant.

摘要翻译： 

多发性骨髓瘤（MM）是一种由环境与遗传因素交互作用导致的多因素遗传性疾病。TP53基因（17p13.1）的正确基因座及其蛋白对维持基因组稳定性至关重要。TP53基因最常见的变异体——p.P72R（rs1042522）——表现出功能多样性。本研究旨在综合分析TP53 p.P72R变异与TP53基因表达，及其与TP53基因座染色体改变、MM患病风险及预后的关联。通过对129例新诊断MM患者的基因组DNA进行自动化DNA测序（用于TP53变异分析）和cIg-FISH（用于染色体畸变分析），并采用实时PCR技术检测RNA中的TP53表达水平。结果显示，MM患者中TP53变异不符合哈迪-温伯格平衡。RR基因型与较低的MM风险相关（OR = 0.44，p = 0.004）。与PP+PR基因型患者相比，RR基因型患者浆细胞数量更高（36.74% vs. 28.30%，p = 0.02）。PP+PR基因型患者的TP53基因表达水平显著高于RR纯合子（p < 0.001），吸烟者表达水平亦高于非吸烟者（p = 0.02）。TP53表达水平与浆细胞数量呈正相关（r = 0.26，p = 0.04）。无论是否涉及TP53基因座，17号染色体畸变的存在均未对MM风险及预后产生影响。TP53基因表达与p.P72R变异的相关分析亦呈现相似结果。

原文链接：

Association of Chromosome 17 Aneuploidy,TP53Deletion, Expression and Its rs1042522 Variant with Multiple Myeloma Risk and Response to Thalidomide/Bortezomib Treatment