Mutations or copy number losses of CD58 and TP53 genes in diffuse large B cell lymphoma are independent unfavorable prognostic factors.
Mutations or copy number losses of CD58 and TP53 genes in diffuse large B cell lymphoma are independent unfavorable prognostic factors.
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弥漫性大B细胞淋巴瘤中CD58和TP53基因的突变或拷贝数丢失是独立的不利预后因素
DOI：
10.18632/oncotarget.13065
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发表时间：
2016-12-13
期刊：
影响因子：
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通讯作者：
Zhou J
中科院分区：
文献类型：
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作者：
Cao Y;Zhu T;Zhang P;Xiao M;Yi S;Yang Y;Li Q;Ling S;Wang Y;Gao L;Zhu L;Wang J;Wang N;Huang L;Zhang P;Zhai Q;Qiu L;Zhou J
下一代测序（NGS）技术的出现加速了弥漫性大B细胞淋巴瘤（DLBCL）中新的基因病变的发现。这些已确定的基因突变的预后意义在很大程度上是未知的。在这项研究中，我们对196例患者中最常涉及的27个基因进行了NGS。有趣的是，发现TP53突变在伴有MYC易位的DLBCL中明显更为常见（r = 0.446，P = 0.034）。虽然在伴有骨髓受累的DLBCL患者中未发现有更普遍的基因突变，但MYD88突变在中枢神经系统或睾丸原发性DLBCL中更为常见。为了评估这27个基因异常的预后意义，共有165例新诊断的非特指型DLBCL患者被纳入多变量生存分析。令人惊讶的是，除了TP53突变外，还发现CD58突变可预测不良的临床结果。此外，CD58或TP53的拷贝数缺失也被确定为一个独立的不良预后因素。我们的研究结果揭示了基因突变对DLBCL预后以前未知的关键影响，对未来设计针对性治疗以改善临床结果具有根本的重要性。
The advent of next generation sequencing (NGS) technologies has expedited the discovery of novel genetic lesions in DLBCL. The prognostic significance of these identified gene mutations is largely unknown. In this study, we performed NGS for the 27 genes most frequently implicated in 196 patients. Interestingly, TP53 mutations were found to be significantly more common in DLBCL with MYC translocations (r = 0.446, P = 0.034). While no gene mutation was found to be more prevalent in patients with DLBCL with bone marrow involvement, MYD88 mutations were more common in primary DLBCL of the CNS or testis. To evaluate the prognostic significance of the abnormalities of these 27 genes, a total of 165 patients with newly diagnosed DLBCL, NOS were included in a multivariate survival analysis. Surprisingly, in addition to the TP53 mutation, CD58 mutation was found to predict poor clinical outcome. Furthermore, copy number loss of CD58 or TP53 was also identified to be an independent negative prognostic factor. Our results have uncovered the previously unknown critical impact of gene mutations on the prognosis of DLBCL and are fundamentally important for the future design of tailored therapy for improved clinical outcomes.