Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid neoplasm in dogs and in humans. It is characterized by a remarkable degree of clinical heterogeneity that is not completely elucidated by molecular data. This poses a major barrier to understanding the disease and its response to therapy, or when treating dogs with DLBCL within clinical trials. We performed an integrated analysis of exome (n = 77) and RNA sequencing (n = 43) data in a cohort of canine DLBCL to define the genetic landscape of this tumor. A wide range of signaling pathways and cellular processes were found in common with human DLBCL, but the frequencies of the most recurrently mutated genes (TRAF3, SETD2, POT1, TP53, MYC, FBXW7, DDX3X and TBL1XR1) differed. We developed a prognostic model integrating exonic variants and clinical and transcriptomic features to predict the outcome in dogs with DLBCL. These results comprehensively define the genetic drivers of canine DLBCL and can be prospectively utilized to identify new therapeutic opportunities.

弥漫性大 B 细胞淋巴瘤 (DLBCL) 是犬和人类最常见的淋巴肿瘤。它的特点是显着程度的临床异质性，分子数据并未完全阐明。这对理解该疾病及其对治疗的反应或在临床试验中用 DLBCL 治疗狗构成了主要障碍。我们对一组犬 DLBCL 中的外显子组 ( n  = 77) 和 RNA 测序 ( n = 43) 数据进行了综合分析， 以确定该肿瘤的遗传景观。在人类 DLBCL 中发现了广泛的信号通路和细胞过程，但突变频率最高的基因（TRAF3、SETD2、POT1、TP53, MYC , FBXW7 , DDX3X和TBL1XR1 ) 不同。我们开发了一个整合外显子变异和临床和转录组学特征的预后模型，以预测患有 DLBCL 的狗的结果。这些结果全面定义了犬 DLBCL 的遗传驱动因素，并可前瞻性地用于确定新的治疗机会。