Asada Hajime, Tsuboi Masaya, Chambers James K, Uchida Kazuyuki, Tomiyasu Hirotaka, Goto-Koshino Yuko, 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 Pathology, Graduate School of Agricultural and Life Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
J Vet Med Sci. 2017 Oct 20;79(10):1721-1726. doi: 10.1292/jvms.17-0197. Epub 2017 Sep 1.
Canine histiocytic sarcoma (HS) is a malignancy originating from the histiocytic cell lineage and characterized by poor response to chemotherapy and short survival time. Mutation of the TP53 gene and its association with poor prognosis has been reported in several canine tumors. However, the mutation of this gene has not been investigated in canine HS. The aim of this study was to examine a TP53 gene mutation in dogs with HS. Aberrations of the TP53 gene were examined by polymerase chain reaction-single strand conformational polymorphism analysis and DNA sequence analysis, revealing mutations of the TP53 gene in 12 (46%) of 26 dogs affected by HS. The incidence of the TP53 gene mutation was relatively high in canine HS compared with other canine tumors. Among these mutations, 10 of 12 dogs (83%) with a TP53 gene mutation harbored the same mutation: a 2-base (AT) insertion in exon 5, resulting in the introduction of a stop codon (c.446_447insAT, p.Tyr150SerfsX8). Further studies are needed to examine the functional change due to the mutation and its association with the pathogenesis of canine HS.
犬组织细胞肉瘤（HS）是一种起源于组织细胞谱系的恶性肿瘤，其特征为对化疗反应不佳且生存时间短。TP53基因突变及其与不良预后的关联已在几种犬类肿瘤中报道。然而，该基因的突变尚未在犬HS中进行研究。本研究的目的是检测患有HS的犬的TP53基因突变。通过聚合酶链反应-单链构象多态性分析和DNA序列分析检测TP53基因的畸变，发现在26只患有HS的犬中有12只（46%）存在TP53基因突变。与其他犬类肿瘤相比，TP53基因突变在犬HS中的发生率相对较高。在这些突变中，12只发生TP53基因突变的犬中有10只（83%）具有相同的突变：外显子5中2个碱基（AT）插入，导致引入一个终止密码子（c.446_447insAT，p.Tyr150SerfsX8）。需要进一步研究以检测该突变引起的功能变化及其与犬HS发病机制的关联。
