Khand Faiz Muhammad, Yao Da-Wei, Hao Pan, Wu Xin-Qi, Kamboh Asghar Ali, Yang De-Ji
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China.
Diagnostics (Basel). 2020 Feb 14;10(2):104. doi: 10.3390/diagnostics10020104.
Early diagnosis of mammary gland tumors is a challenging task in animals, especially in unspayed dogs. Hence, this study investigated the role of microsatellite instability (MSI), MMR gene mRNA transcript levels and SNPs of MMR genes in canine mammary gland tumors (CMT). A total of 77 microsatellite (MS) markers in 23 primary CMT were selected from four breeds of dogs. The results revealed that 11 out of 77 MS markers were unstable and showed MSI in all the tumors (at least at one locus), while the other markers were stable. Compared to the other markers, the ABC9TETRA, MEPIA, 9A5, SCNA11 and FJL25 markers showed higher frequencies of instability. All CMT demonstrated MSI, with eight tumors presenting MSI-H. The RT-qPCR results revealed significant upregulation of the mRNA levels of , , and , but downregulation of compared to the levels in the control group. Moreover, single nucleotide polymorphisms (SNPs) were observed in the gene in four exons, i.e., 2, 6, 15, and 16. In conclusion, MSI, overexpression of MMR genes and SNPs in the MMR gene are associated with CMT and could be served as diagnostic biomarkers for CMT in the future.
乳腺肿瘤的早期诊断在动物中是一项具有挑战性的任务,尤其是在未绝育的犬类中。因此,本研究调查了微卫星不稳定性(MSI)、错配修复(MMR)基因mRNA转录水平以及MMR基因单核苷酸多态性(SNP)在犬乳腺肿瘤(CMT)中的作用。从四个犬种的23个原发性CMT中总共选择了77个微卫星(MS)标记。结果显示,77个MS标记中有11个不稳定,并且在所有肿瘤中(至少在一个位点)表现出MSI,而其他标记是稳定的。与其他标记相比,ABC9TETRA、MEPIA、9A5、SCNA11和FJL25标记显示出更高的不稳定性频率。所有CMT均表现出MSI,其中8个肿瘤表现为高度微卫星不稳定(MSI-H)。逆转录定量聚合酶链反应(RT-qPCR)结果显示,与对照组相比, 、 和 的mRNA水平显著上调,但 下调。此外,在 基因的四个外显子(即2、6、15和16)中观察到单核苷酸多态性(SNP)。总之,MSI、MMR基因的过表达以及MMR基因中的SNP与CMT相关,并且未来可作为CMT的诊断生物标志物。