Frantz A M, Sarver A L, Ito D, Phang T L, Karimpour-Fard A, Scott M C, Valli V E O, Lindblad-Toh K, Burgess K E, Husbands B D, Henson M S, Borgatti A, Kisseberth W C, Hunter L E, Breen M, O'Brien T D, Modiano J F
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, Minnesota, USA.
Vet Pathol. 2013 Jul;50(4):693-703. doi: 10.1177/0300985812465325. Epub 2012 Nov 2.
We performed genomewide gene expression analysis of 35 samples representing 6 common histologic subtypes of canine lymphoma and bioinformatics analyses to define their molecular characteristics. Three major groups were defined on the basis of gene expression profiles: (1) low-grade T-cell lymphoma, composed entirely by T-zone lymphoma; (2) high-grade T-cell lymphoma, consisting of lymphoblastic T-cell lymphoma and peripheral T-cell lymphoma not otherwise specified; and (3) B-cell lymphoma, consisting of marginal B-cell lymphoma, diffuse large B-cell lymphoma, and Burkitt lymphoma. Interspecies comparative analyses of gene expression profiles also showed that marginal B-cell lymphoma and diffuse large B-cell lymphoma in dogs and humans might represent a continuum of disease with similar drivers. The classification of these diverse tumors into 3 subgroups was prognostically significant, as the groups were directly correlated with event-free survival. Finally, we developed a benchtop diagnostic test based on expression of 4 genes that can robustly classify canine lymphomas into one of these 3 subgroups, enabling a direct clinical application for our results.
我们对代表犬淋巴瘤6种常见组织学亚型的35个样本进行了全基因组基因表达分析,并进行了生物信息学分析以确定其分子特征。根据基因表达谱定义了三个主要组:(1)低级别T细胞淋巴瘤,完全由T区淋巴瘤组成;(2)高级别T细胞淋巴瘤,由淋巴母细胞性T细胞淋巴瘤和未另行指定的外周T细胞淋巴瘤组成;(3)B细胞淋巴瘤,由边缘B细胞淋巴瘤、弥漫性大B细胞淋巴瘤和伯基特淋巴瘤组成。基因表达谱的种间比较分析还表明,犬和人类的边缘B细胞淋巴瘤和弥漫性大B细胞淋巴瘤可能代表具有相似驱动因素的疾病连续体。将这些不同的肿瘤分为3个亚组在预后方面具有重要意义,因为这些组与无事件生存期直接相关。最后,我们基于4个基因的表达开发了一种台式诊断测试,该测试可以将犬淋巴瘤可靠地分类为这3个亚组之一,从而使我们的结果能够直接应用于临床。