Whole-exome sequencing analysis identifies distinct mutational profile and novel prognostic biomarkers in primary gastrointestinal diffuse large B-cell lymphoma.
Whole-exome sequencing analysis identifies distinct mutational profile and novel prognostic biomarkers in primary gastrointestinal diffuse large B-cell lymphoma.
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全外显子组测序分析确定了原发性胃肠道弥漫性大 B 细胞淋巴瘤的独特突变谱和新的预后生物标志物
DOI：
10.1186/s40164-022-00325-7
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发表时间：
2022-10-15
影响因子：
10.9
通讯作者：
Xiao, Jian
中科院分区：
文献类型：
--
作者：
Li, Shan-Shan;Zhai, Xiao-Hui;Liu, Hai-Ling;Liu, Ting-Zhi;Cao, Tai-Yuan;Chen, Dong-Mei;Xiao, Le-Xin;Gan, Xiao-Qin;Cheng, Ke;Hong, Wan-Jia;Huang, Yan;Lian, Yi-Fan;Xiao, Jian
关键词：
弥漫性大B细胞淋巴瘤（DLBCL）是最常见的侵袭性非霍奇金淋巴瘤，约10%的DLBCL病例主要发生在胃肠道。先前的报道已经揭示了原发性胃肠道DLBCL（pGI-DLBCL）具有与其他结或淋巴结DLBCL不同的基因突变。然而，pGI-DLBCL的外显子突变谱尚未完全解决。我们对来自53名pGI-DLBCL患者的匹配肿瘤组织和血液样本进行了全外显子组测序。筛选外显子突变谱，分析基因突变与临床病理特征的相关性。总共发现了6，588个蛋白质改变事件，并且在我们的pGI-DLBCL群组中五个最常见的突变基因是IGLL 5（47%）、TP 53（42%）、BTG 2（28%）、P2 RY 8（26%）和PCLO（23%）。与普通DLBCL相比，在pGI-DLBCL中鉴定出显著较少或不存在MYD 88（0%）、EZH 2（0%）、BCL 2（2%）或CD 79 B（8%）突变。复发性潜在驱动基因主要富集在与信号转导、感染性疾病和免疫调节相关的通路中。此外，HBV感染对pGI-DLBCL中的突变特征有影响，因为HBsAg阳性与TP 53和LRP 1B突变显著相关，这两种突变是许多人类癌症中确定的肿瘤抑制基因。此外，IGLL 5和LRP 1B突变与患者总生存期显著相关，可作为pGI-DLBCL中两种新的预后生物标志物。我们的研究提供了迄今为止最大的pGI-DLBCL队列的外显子突变谱的全面视图。这些结果可以促进pGI-DLBCL新的治疗和预后生物标志物的临床开发。在线版本包含补充材料，可通过10.1186/s40164-022-00325-7获得。
Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma, and about 10% of DLBCL cases primarily occur in the gastrointestinal tract. Previous reports have revealed that primary gastrointestinal-DLBCL (pGI-DLBCL) harbors different genetic mutations from other nodal or extranodal DLBCL. However, the exonic mutation profile of pGI-DLBCL has not been fully addressed. We performed whole-exome sequencing of matched tumor tissues and blood samples from 53 pGI-DLBCL patients. The exonic mutation profiles were screened, and the correlations between genetic mutations and clinicopathological characteristics were analyzed. A total of 6,588 protein-altering events were found and the five most frequent mutated genes in our pGI-DLBCL cohort were IGLL5 (47%), TP53 (42%), BTG2 (28%), P2RY8 (26%) and PCLO (23%). Compared to the common DLBCL, significantly less or absence of MYD88 (0%), EZH2 (0%), BCL2 (2%) or CD79B (8%) mutations were identified in pGI-DLBCL. The recurrent potential driver genes were mainly enriched in pathways related to signal transduction, infectious disease and immune regulation. In addition, HBV infection had an impact on the mutational signature in pGI-DLBCL, as positive HBsAg was significantly associated with the TP53 and LRP1B mutations, two established tumor suppressor genes in many human cancers. Moreover, IGLL5 and LRP1B mutations were significantly correlated with patient overall survival and could serve as two novel prognostic biomarkers in pGI-DLBCL. Our study provides a comprehensive view of the exonic mutation profile of the largest pGI-DLBCL cohort to date. The results could facilitate the clinical development of novel therapeutic and prognostic biomarkers for pGI-DLBCL. The online version contains supplementary material available at 10.1186/s40164-022-00325-7.
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