Genetic lesions in MYC and STAT3 drive oncogenic transcription factor overexpression in plasmablastic lymphoma.
Genetic lesions in MYC and STAT3 drive oncogenic transcription factor overexpression in plasmablastic lymphoma.
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DOI：
10.3324/haematol.2020.251579
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发表时间：
2021-04-01
期刊：
影响因子：
10.1
通讯作者：
Montes-Moreno S
中科院分区：
文献类型：
--
作者：
Garcia-Reyero J;Martinez Magunacelaya N;Gonzalez de Villambrosia S;Loghavi S;Gomez Mediavilla A;Tonda R;Beltran S;Gut M;Pereña Gonzalez A;d'Ámore E;Visco C;Khoury JD;Montes-Moreno S
浆母细胞淋巴瘤的突变特征尚未被描述。我们对30例浆母细胞淋巴瘤患者进行了有针对性的外显子下一代测序分析，并用B细胞淋巴瘤专属小组和荧光原位杂交检测MYC重排。肿瘤和微环境细胞群体的完整表型也被进行了。我们发现MYC(69%的MYC易位或扩增和3例错义点突变)、PRDM1/Blimp1和STAT3突变的复发遗传事件丰富。这些基因突变在EB病毒(EBV)阳性的疾病中更为常见。其他遗传事件包括BRAF、EP300、BCR(CD79A和CD79B)、Noch途径(NOTCH2、NOTCH1和SGK1)和MYD88pL265P突变。免疫组织化学分析显示一致的MYC表达，在MYC重排的病例中表达较高，在STAT3 SH2区域突变的病例中有磷酸化STAT3(Tyr705)的过度表达。微环境细胞群是异质性的，与EB病毒无关，肿瘤相关巨噬细胞()和PD1阳性T细胞丰富。PD-L1在人群中全部表达，但仅在5例肿瘤细胞中表达(14例EB病毒阳性中4例)。在大多数浆母细胞淋巴瘤中，HL A表达缺失。综上所述，浆母细胞淋巴瘤的突变特征是异质性的，并且与EBV感染有关。在EBV阳性的疾病中，MYC、STAT3和PRDM1/Blimp1基因事件更为常见。在浆母细胞淋巴瘤的微环境中，和PD1反应性T淋巴细胞大量聚集，部分肿瘤细胞表达PD-L1。
The mutational profile of plasmablastic lymphoma has not been described. We performed a targeted, exonic next-generation sequencing analysis of 30 plasmablastic lymphoma cases with a Bcell lymphoma-dedicated panel and fluorescence in situ hybridization for the detection of MYC rearrangements. Complete phenotyping of the neoplastic and microenvironmental cell populations was also performed. We identified an enrichment in recurrent genetic events in MYC (69% with MYC translocation or amplification and three cases with missense point mutations), PRDM1/Blimp1 and STAT3 mutations. These gene mutations were more frequent in Epstein-Barr virus (EBV)-positive disease. Other genetic events included mutations in BRAF, EP300, BCR (CD79A and CD79B), NOTCH pathway (NOTCH2, NOTCH1 and SGK1) and MYD88pL265P. Immunohistochemical analysis showed consistent MYC expression, which was higher in cases with MYC rearrangements, together with phospho-STAT3 (Tyr705) overexpression in cases with STAT3 SH2 domain mutations. Microenvironmental cell populations were heterogeneous and unrelated to EBV, with enrichment of tumor-associated macrophages (TAM) and PD1-positive T cells. PD-L1 was expressed in all cases in the TAM population but only in the neoplastic cells in five cases (4 of 14 EBV-positive cases). HLA expression was absent in the majority of cases of plasmablastic lymphoma. In summary, the mutational profile of plasmablastic lymphoma is heterogeneous and related to EBV infection. Genetic events in MYC, STAT3 and PRDM1/Blimp1 are more frequent in EBV-positive disease. An enrichment in TAM and PD1 reactive T lymphocytes is found in the microenvironment of plasmablastic lymphoma and a fraction of the neoplastic cells express PD-L1.
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DOI：
10.1038/modpathol.2010.72
发表时间：
2010-07
期刊：
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
影响因子：
--
作者：
Taddesse-Heath L;Meloni-Ehrig A;Scheerle J;Kelly JC;Jaffe ES
通讯作者：
Jaffe ES
影响因子：
28.5
作者：
Loghavi S;Alayed K;Aladily TN;Zuo Z;Ng SB;Tang G;Hu S;Yin CC;Miranda RN;Medeiros LJ;Khoury JD
通讯作者：
Khoury JD
影响因子：
7.5
作者：
Montes-Moreno, Santiago;Martinez-Magunacelaya, Nerea;Piris, Miguel A.
通讯作者：
Piris, Miguel A.
影响因子：
20.3
作者：
Sarosiek, Kristopher A.;Malumbres, Raquel;Lossos, Izidore S.
通讯作者：
Lossos, Izidore S.
DOI：
10.1158/1078-0432.ccr-13-0855
发表时间：
2013-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Chen BJ;Chapuy B;Ouyang J;Sun HH;Roemer MG;Xu ML;Yu H;Fletcher CD;Freeman GJ;Shipp MA;Rodig SJ
通讯作者：
Rodig SJ