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Abstract：
Primary testicular lymphoma (PTL) is a rare lymphoma predominantly occurring in the elderly male population. It is characterized by a limited response to treatment and a heightened tendency towards relapse. Histologically, approximately 90% of PTL cases are classified as diffuse large B-cell lymphomas (DLBCL). Genetic features of PTL were delineated in a limited scope within several independent studies. Some of the articles which analyzed the genetic characterization of DLBCL have incorporated PTL samples, but these have been constrained by small sample sizes. In addition, there have been an absence of independent molecular typing studies of PTL. This report summarizes the common mutational features, copy number variations (CNVs) and molecular typing of PTL patients, based on whole-exome sequencing (WES) conducted on a cohort of 25 PTL patients. Among them, HLA, CDKN2A and MYD88 had a high mutation frequency. In addition, we found two core mutational characteristics in PTL including mutation in genes linked to genomic instability (TP53 and CDKN2A) and mutation in immune-related genes (HLA, MYD88, CD79B). We performed molecular typing of 25 PTL patients into C1 subtype with predominantly TP53 mutations and C2 subtype with predominantly HLA mutations. Notably, mutations in the TP53 gene predicted a poor outcome in most types of lymphomas. However, the C1 subtype, dominated by TP53 mutations, had a better prognosis compared to the C2 subtype in PTL. C2 subtype exhibited a worse prognosis, aligning with our finding that the mechanism of immune escape in PTL was primarily the deletions of HLA rather than PD-L1/PD-L2 alterations, a contrast to other DLBCLs. Moreover, we calculated the tumor mutation burden (TMB) and identified that TMB can predict prognosis and recurrence rate in PTL. Our study underscores the significance of molecular typing in PTL based on mutational characteristics, which plays a crucial role in prognostication and guiding therapeutic strategies for patients.
摘要：
原发性睾丸淋巴瘤（PTL）是一种罕见的淋巴瘤，主要发生在老年男性人群中。它的特点是对治疗的反应有限，复发的趋势加剧。组织学上,大约90%的PTL病例被分类为弥漫性大B细胞淋巴瘤(DLBCL).在几项独立研究中，PTL的遗传特征在有限的范围内进行了描述。一些分析DLBCL遗传特征的文章已经纳入了PTL样本，但这些都受到小样本量的限制。此外,目前尚无PTL的独立分子分型研究.本报告总结了常见的突变特征，PTL患者的拷贝数变异（CNVs）和分子分型，基于对25名PTL患者进行的全外显子组测序（WES）。其中,HLA,CDKN2A和MYD88突变频率高。此外,我们发现PTL的两个核心突变特征，包括与基因组不稳定性相关的基因突变（TP53和CDKN2A）和免疫相关基因的突变（HLA，MYD88,CD79B)。我们对25例PTL患者进行了分子分型，分为主要为TP53突变的C1亚型和主要为HLA突变的C2亚型。值得注意的是,TP53基因突变预测大多数类型淋巴瘤的预后较差.然而,C1亚型，以TP53突变为主，与PTL中的C2亚型相比，预后更好。C2亚型预后较差，与我们的发现一致，即PTL中免疫逃逸的机制主要是HLA的缺失，而不是PD-L1/PD-L2改变，与其他DLBCL形成对比。此外，我们计算了肿瘤突变负荷(TMB),发现TMB可以预测PTL的预后和复发率.我们的研究强调了基于突变特征的PTL分子分型的重要性，这在患者的预后和指导治疗策略中起着至关重要的作用。
