Center of Excellence for Companion Animal Cancer, Department of Pathology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand.
Clemson Veterinary Diagnostic Center, Clemson University, Columbia, SC, USA.
Sci Rep. 2022 Mar 24;12(1):5120. doi: 10.1038/s41598-022-09112-0.
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of lymphoma in dogs with a multicentric form. This study aimed to assemble 41 variants of the previously reported genes and to investigate these variants in canine DLBCL using the Agena MassARRAY platform. These variants were chosen based on the high prevalence observed in canine B- and T-cell lymphomas, their significance for target therapy, and compatibility for multiplex PCR amplification. Lymph node biopsy was performed from 60 dogs with B-cell lymphoma comprising 47 purebred and 13 crossbred dogs. All dogs presented single nucleotide polymorphisms (SNPs) at HYAL4 and SATB1 genes. The lesser mutual SNPs were observed at SEL1L, excluding a cocker spaniel, and c-Kit, with the exception of a pug and a French bulldog. Even though no statistical association was noted between each SNP and dog breed, purebreds were 3.88 times more likely to have a SNP at FLT3 rs852342480 (95%CI 0.50-45.03, p = 0.26), 3.64 times at TRAF3 F306X (95%CI 0.58-42.50, p = 0.43) and 2.66 times at TRAF3 E303EX (95%CI 0.56-13.12, p = 0.31). Also, DLBCL dogs (CHOP-based treatment) with c-Kit T425= had a poorer prognosis with shorter median overall survival times (OST) than dogs with the wild type. Dogs treated with COP chemotherapy and contained 3-5 variants at SEL1L were associated with decreased median OST. Therefore, this SNP's lymphoma panel provides valuable information that we can use to outline a prognosis and develop a treatment plan for the targeted therapy of each dog.
弥漫性大 B 细胞淋巴瘤（DLBCL）是犬最常见的淋巴瘤亚型，呈多中心形式。本研究旨在组装先前报道基因的 41 种变体，并使用 Agena MassARRAY 平台研究这些变体在犬 DLBCL 中的作用。这些变体是基于犬 B 和 T 细胞淋巴瘤中的高患病率、对靶向治疗的重要性以及用于多重 PCR 扩增的兼容性而选择的。对 60 只患有 B 细胞淋巴瘤的犬进行了淋巴结活检，其中 47 只为纯种犬，13 只为杂种犬。所有犬均在 HYAL4 和 SATB1 基因中存在单核苷酸多态性（SNP）。在 SEL1L 中观察到较少的共同 SNP，除了一只可卡犬和一只法国斗牛犬外，还排除了 c-Kit 基因。尽管没有注意到每个 SNP 与犬种之间存在统计学关联，但纯种犬更有可能在 FLT3 rs852342480 （95%CI 0.50-45.03，p=0.26）、TRAF3 F306X （95%CI 0.58-42.50，p=0.43）和 TRAF3 E303EX （95%CI 0.56-13.12，p=0.31）中有 SNP，几率分别为 3.88 倍、3.64 倍和 2.66 倍。此外，与野生型相比，携带 c-Kit T425=的 DLBCL 犬（基于 CHOP 的治疗）预后较差，中位总生存时间（OST）较短。接受 COP 化疗且在 SEL1L 中含有 3-5 种变体的犬与中位 OST 降低相关。因此，该 SNP 的淋巴瘤面板提供了有价值的信息，我们可以利用这些信息来为每只犬勾勒出预后，并制定靶向治疗计划。
