Pediatric brain tumors are often noted to be different from their adult counterparts in terms of molecular features. Primary CNS lymphomas (PCNSLs) are mostly found in elderly adults and are uncommon in children and teenagers. There has only been scanty information about the molecular features of PCNSLs at a young age. We examined PCNSLs in 34 young patients aged between 7 and 39 years for gene rearrangements of BCl2, BCL6, CCND1, IRF4, IGH, IGL, IGK, and MYC, homozygous deletions (HD) of CDKN2A, and HLA by FISH. Sequencing was performed using WES, panel target sequencing, or Sanger sequencing due to the small amount of available tissues. The median OS was 97.5 months and longer than that for older patients with PCNSLs. Overall, only 14 instances of gene rearrangement were found (5%), and patients with any gene rearrangement were significantly older (p= 0.029). CDKN2A HD was associated with a shorter OS (p< 0.001). Only 10/31 (32%) showed MYD88 mutations, which were not prognostically significant, and only three of them were L265P mutations. CARD11 mutations were found in 8/24 (33%) cases only. Immunophenotypically, the cases were predominantly GCB, in contrast to older adults (61%). In summary, we showed that molecular findings identified in the PCNSLs of the older patients were only sparingly present in pediatric and young adult patients.
在分子特征方面，儿童脑肿瘤通常与成人脑肿瘤存在差异。原发性中枢神经系统淋巴瘤（PCNSLs）多见于老年人群，在儿童和青少年中较为罕见。关于年轻患者PCNSLs的分子特征，目前仅有少量研究数据。本研究通过荧光原位杂交技术检测了34例年龄在7至39岁之间的年轻PCNSLs患者的BCl2、BCL6、CCND1、IRF4、IGH、IGL、IGK和MYC基因重排情况，以及CDKN2A纯合性缺失和HLA状态。由于可用组织样本量有限，采用全外显子组测序、靶向测序或Sanger测序进行基因分析。患者中位总生存期为97.5个月，较老年PCNSLs患者更长。总体而言，仅发现14例基因重排（占5%），且存在基因重排的患者年龄显著更大（p=0.029）。CDKN2A纯合性缺失与较短的总生存期相关（p<0.001）。31例患者中仅10例（32%）检出MYD88突变，且该突变无预后意义，其中仅3例为L265P突变。24例患者中8例（33%）检出CARD11突变。免疫表型分析显示，与老年患者（61%）不同，本研究病例以生发中心B细胞型为主。综上所述，本研究表明老年PCNSLs患者中常见的分子特征在儿童及年轻成人患者中较为少见。
The Molecular Landscape of Primary CNS Lymphomas (PCNSLs) in Children and Young Adults
肿瘤(癌症)患者之家