睾丸大B细胞淋巴瘤在遗传学上与原发中枢神经系统淋巴瘤（PCNSL）相似，且不同于结节性弥漫大B细胞淋巴瘤（DLBCL）

Testicular large B-cell lymphoma is genetically similar to PCNSL and distinct from nodal DLBCL

HemaSphere

影响因子:14.6

分区:医学3区 / 血液学3区

发表日期:2024 Oct

作者: Alfredo Rivas-Delgado, Cristina López, Guillem Clot, Ferran Nadeu, Marta Grau, Gerard Frigola, Jan Bosch-Schips, Josefine Radke, Naveed Ishaque, Miguel Alcoceba, Gustavo Tapia, Luis Luizaga, Carmen Barcena, Nicholas Kelleher, Neus Villamor, Tycho Baumann, Ana Muntañola, Juan M Sancho-Cia, Alejandro M García-Sancho, Eva Gonzalez-Barca, Estella Matutes, Jordi A Brito, Kennosuke Karube, Itziar Salaverria, Anna Enjuanes, Stefan Wiemann, Frank L Heppner, Reiner Siebert, Fina Climent, Elías Campo, Eva Giné, Armando López-Guillermo, Silvia Beà

DOI: 10.1002/hem3.70024

摘要

睾丸大B细胞淋巴瘤（TLBCL）是一种罕见且侵袭性强的淋巴瘤，起源于免疫特权部位，近期被认定为不同于弥漫性大B细胞淋巴瘤（DLBCL）的独立实体。本文描述了TLBCL的遗传特征，并与已发表的结节性DLBCL和原发性中枢神经系统大B细胞淋巴瘤（PCNSL）的系列进行了比较。我们收集了61例TLBCL患者样本，采用靶向新一代测序、拷贝数分析和荧光原位杂交（FISH）技术评估40例有材料的病例的染色体重排情况。研究发现，70%的病例处于局部期。BCL6重排在36%的病例中检测到，没有同时存在BCL2和MYC重排。TLBCL的拷贝数变化较少（p<0.04），但体细胞变异更多（p<0.02），且更常见18q21.32-q23（BCL2）的扩增，以及6q和9p21.3（CDKN2A/B）的缺失。PIM1、MYD88 L265P、CD79B、TBL1XR1、MEF2B、CIITA、EP300和ETV6突变在TLBCL中更为频繁，而结节性DLBCL中BCL10突变较多。TLBCL与PCNSL之间未见显著的遗传差异。局部或弥散性TLBCL表现出相似的基因组特征。利用LymphGen分类，大部分病例归为MCD亚型，但也观察到一部分患者归为BN2亚型，表明TLBCL的遗传谱具有一定的异质性。TLBCL的基因特征与PCNSL相似，支持其作为一个独立于DLBCL的实体的认定，并可能为靶向治疗策略提供信息。

Abstract

Testicular large B-cell lymphoma (TLBCL) is an infrequent and aggressive lymphoma arising in an immune-privileged site and has recently been recognized as a distinct entity from diffuse large B-cell lymphoma (DLBCL). We describe the genetic features of TLBCL and compare them with published series of nodal DLBCL and primary large B-cell lymphomas of the CNS (PCNSL). We collected 61 patients with TLBCL. We performed targeted next-generation sequencing, copy number arrays, and fluorescent in situ hybridization to assess chromosomal rearrangements in 40 cases with available material. Seventy percent of the cases showed localized stages. BCL6 rearrangements were detected in 36% of cases, and no concomitant BCL2 and MYC rearrangements were found. TLBCL had fewer copy number alterations (p < 0.04) but more somatic variants (p < 0.02) than nodal DLBCL and had more frequent 18q21.32-q23 (BCL2) gains and 6q and 9p21.3 (CDKN2A/B) deletions. PIM1, MYD88 L265P , CD79B, TBL1XR1, MEF2B, CIITA, EP300, and ETV6 mutations were more frequent in TLBCL, and BCL10 mutations in nodal DLBCL. There were no major genetic differences between TLBCL and PCNSL. Localized or disseminated TLBCL displayed similar genomic profiles. Using LymphGen, the majority of cases were classified as MCD. However, we observed a subgroup of patients classified as BN2, both in localized and disseminated TLBCL, suggesting a degree of genetic heterogeneity in the TLBCL genetic profile. TLBCL has a distinctive genetic profile similar to PCNSL, supporting its recognition as a separate entity from DLBCL and might provide information to devise targeted therapeutic approaches.