睾丸大B细胞淋巴瘤在遗传上与PCNSL相似，与淋巴结DLBCL不同
Testicular large B-cell lymphoma is genetically similar to PCNSL and distinct from nodal DLBCL
影响因子:14.60000
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
摘要
睾丸大B细胞淋巴瘤（TLBCL）是一种在免疫特性部位出现的很少且侵袭性的淋巴瘤，最近被认为是与弥漫性大B细胞淋巴瘤（DLBCL）的独特实体。我们描述了TLBCL的遗传特征，并将其与CNS（PCNSL）的一系列淋巴结DLBCL和一系列大型B细胞淋巴瘤进行了比较。我们收集了61例TLBCL患者。我们进行了针对性的下一代测序，拷贝数阵列和原位杂交，以评估40例可用材料的40例染色体重排。 70％的案件显示局部阶段。在36％的病例中检测到BCl6重排，并且没有伴随的BCL2，并且发现MYC重排。 TLBCL的拷贝数变化较少（p <0.04），但体细胞变体（p <0.02）的次数比Nodal DLBCL更频繁，并且更频繁的18q21.32-Q23（BCl2）增益和6Q和9P21.3（CDKN2A/b）的增加。 PIM1，MYD88 L265P，CD79B，TBL1XR1，MEF2B，CIITA，EP300和ETV6突变在TLBCL中更频繁，而Nodal DLBCL中的BCl10突变更为频繁。 TLBCL和PCNSL之间没有主要的遗传差异。局部或传播的TLBCL显示出相似的基因组轮廓。使用淋巴，大多数病例被归类为MCD。然而，我们观察到属于局部和散布的TLBCL的一组被归类为BN2的患者的亚组，这表明TLBCL遗传特征中有一定程度的遗传异质性。 TLBCL具有与PCNSL相似的独特遗传特征，支持其作为与DLBCL独立实体的识别，并可能提供信息来设计有针对性的治疗方法。
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.