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在带有EZH2表达的地幔细胞淋巴瘤中,TP53突变很常见,当两者都存在时,结果很糟糕

Do Hwan Kim¹, Saima Siddiqui¹, Preetesh Jain²

¹Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

Human pathology

|March 9, 2024

概括

在地幔细胞淋巴瘤 (MCL) 中增强质同类素2 (EZH2) 表达与TP53突变和侵袭性疾病特征相关. 结合EZH2表达或TP53突变表明预后不佳,当两者都存在时,结果令人丧.

科学领域:

在瘤学瘤学.
血液学血液学血液学
分子生物学分子生物学

背景情况:

增强质同源2 (EZH2) 在大约40%的地幔细胞淋巴瘤 (MCL) 病例中表达.
EZH2表达与侵袭性组织学,高增殖率 (Ki-67),p53异常和降低整体存活率 (OS) 有关.

研究的目的:

使用向基因小组研究EZH2表达性MCL (EZH2+ MCL) 的分子格局.
探索EZH2表达,TP53突变和MCL中的临床病理特征之间的关系.

主要方法:

使用了11个基因的下一代测序面板 (包括ATM,BIRC3,CCND1,KMT2C,KMT2D,NOTCH1,NOTCH2,RB1,TP53,TRAF2,UBR5).
进行免疫组织化学评估p53突变模式.
与临床数据相关的分子发现,包括组织学和Ki-67增殖指数.

主要成果:

与EZH2阴性MCL相比,EZH2+MCL表现出TP53突变的频率更高 (41.2%对19.1%,p=0.045).
TP53突变和EZH2表达之间的重叠特征包括侵略性组织学,高Ki-67和p53突变模式.
不管TP53突变状态如何,EZH2表达与高Ki-67相关.
侵略性组织学与EZH2表达或TP53突变有关,可能通过独立的途径.

结论:

在表达EZH2的MCL中,TP53突变更为常见,并为p53突变表型作出贡献.
无论是EZH2表达还是TP53突变,都独立地与MCL的侵袭性疾病和劣质结局有关.
EZH2表达和TP53突变的同时发生意味着MCL患者的预后特别糟糕.

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