Asada Hajime, Tomiyasu Hirotaka, Okada Kazuki, Chambers James K, Goto-Koshino Yuko, Uchida Kazuyuki, Kagawa Yumiko, Ohno Koichi, Tsujimoto Hajime
Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
Res Vet Sci. 2019 Jun;124:57-60. doi: 10.1016/j.rvsc.2019.03.003. Epub 2019 Mar 5.
Canine histiocytic sarcoma (HS) is an aggressive tumor type originating from dendritic cells or macrophages. We previously reported high incidence of the two-base (AT) insertion mutation (insAT) in the tumor protein p53 (TP53) gene in dogs with HS, and the aim of this study was to investigate the clinical significance of insAT in canine HS. The present study established a sensitive digital PCR-based assay for detecting insAT and examined its associations with clinical variables and survival time. The mutation was detected in 26 of 64 dogs (41%), and the mean mutant allele frequency was 1.9% (range, 0.014-35%), indicating that not all tumor cells harbor insAT. The incidence of insAT was significantly higher in dogs with metastatic lesions than in those without metastatic lesions. However, the existence of insAT was not associated with survival time or response to chemotherapy with lomustine or nimustine. This study suggested that HS cells might acquire insAT in the TP53 gene during development of metastasis, but insAT was not a prognostic factor in canine HS. Further studies are needed to investigate the contribution of insAT to the development of metastatic lesions of canine HS.
犬组织细胞肉瘤（HS）是一种起源于树突状细胞或巨噬细胞的侵袭性肿瘤类型。我们之前报道过患有HS的犬肿瘤蛋白p53（TP53）基因中两碱基（AT）插入突变（insAT）的高发生率，本研究的目的是调查insAT在犬HS中的临床意义。本研究建立了一种基于数字PCR的灵敏检测方法来检测insAT，并研究其与临床变量和生存时间的关联。在64只犬中的26只（41%）检测到该突变，平均突变等位基因频率为1.9%（范围为0.014 - 35%），这表明并非所有肿瘤细胞都携带insAT。有转移病灶的犬中insAT的发生率显著高于无转移病灶的犬。然而，insAT的存在与生存时间或对洛莫司汀或尼莫司汀化疗的反应无关。本研究表明，HS细胞可能在转移发生过程中获得TP53基因中的insAT，但insAT不是犬HS的预后因素。需要进一步研究来调查insAT对犬HS转移病灶发展的作用。
