Department of Medical Informatics and Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, 06591, South Korea.
Department of Biomedical Systems Informatics and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, 03722, South Korea.
Nat Commun. 2020 Jul 17;11(1):3616. doi: 10.1038/s41467-020-17458-0.
Genomic and precision medicine research has afforded notable advances in human cancer treatment, yet applicability to other species remains uncertain. Through whole-exome and transcriptome analyses of 191 spontaneous canine mammary tumors (CMTs) that exhibit the archetypal features of human breast cancers, we found a striking resemblance of genomic characteristics including frequent PIK3CA mutations (43.1%), aberrations of the PI3K-Akt pathway (61.7%), and key genes involved in cancer initiation and progression. We also identified three gene expression-based CMT subtypes, one of which segregated with basal-like human breast cancer subtypes with activated epithelial-to-mesenchymal transition, low claudin expression, and unfavorable disease prognosis. A relative lack of ERBB2 amplification and Her2-enrichment subtype in CMT denoted species-specific molecular mechanisms. Taken together, our results elucidate cross-species oncogenic signatures for a better understanding of universal and context-dependent mechanisms in breast cancer development and provide a basis for precision diagnostics and therapeutics for domestic dogs.
基因组学和精准医学研究为人类癌症治疗带来了显著进展，但在其他物种中的适用性仍不确定。通过对 191 例具有人类乳腺癌典型特征的自发性犬乳腺肿瘤（CMT）进行全外显子组和转录组分析，我们发现了包括 PIK3CA 突变（43.1%）在内的基因组特征惊人相似、PI3K-Akt 通路异常（61.7%）以及涉及癌症发生和进展的关键基因。我们还鉴定了三种基于基因表达的 CMT 亚型，其中一种与基底样人乳腺癌亚型分离，具有激活的上皮-间充质转化、低 Claudin 表达和不良的疾病预后。CMT 中相对缺乏 ERBB2 扩增和 Her2 富集亚型表明存在物种特异性的分子机制。综上所述，我们的研究结果阐明了跨物种致癌特征，有助于更好地理解乳腺癌发生中的普遍和依赖于背景的机制，并为犬类的精准诊断和治疗提供了基础。
