Abstract:
BRAF is one of multiple RAF proteins responsible for the activation of the MAPK cell signalling cascade involved in cell growth, differentiation, and survival. A hotspot BRAFV600E mutation, in exon 15, was determined to be a driver in 100% hairy cell leukaemias, 50%-60% of human melanomas, 30%-50% of human thyroid carcinomas and 10%-20% of human colorectal carcinomas. The orthologous BRAFV595E mutation was seen in 67% and 80% of canine bladder transitional cell carcinomas and prostatic adenocarcinomas, respectively. Since veterinary and human cancers exploit similar pathways and BRAF is highly conserved across species, BRAF can be expected to be a driver in a feline cancer. Primers were developed to amplify exon 15 of feline BRAF. One hundred ninety-six feline tumours were analysed. Sanger sequencing of the 211 bp PCR amplicon was done. A BRAF mutation was found in one tumour, a cutaneous melanoma. The mutation was a BRAFV597E mutation, orthologous to the canine and human hotspot mutations. A common synonymous variant, BRAFT586T, was seen in 23% (47/196) of tumours. This variant was suspected to be a single nucleotide polymorphism. BRAF was not frequently mutated in common feline tumours or in tumour types that frequently harbour BRAF mutations in human and canine cancers. As is seen in canine cancer genomics, the mutational profile in feline tumours may not parallel the histologic equivalent in human oncology.
摘要:
BRAF是多种RAF蛋白之一,负责激活参与细胞生长的MAPK细胞信号级联,分化,和生存。热点BRAFV600E突变,在外显子15中,被确定为100%毛细胞白血病的驱动因素,50%-60%的人黑色素瘤,30%-50%的人类甲状腺癌和10%-20%的人类结直肠癌。在67%和80%的犬膀胱移行细胞癌和前列腺腺癌中观察到直系同源BRAFV595E突变,分别。由于兽医和人类癌症利用相似的途径,并且BRAF在物种之间高度保守,BRAF有望成为猫科动物癌症的驱动因素。开发引物以扩增猫科动物BRAF的外显子15。分析了96个猫科动物肿瘤。完成211bpPCR扩增子的Sanger测序。在一个肿瘤中发现了BRAF突变,皮肤黑色素瘤.突变为BRAFV597E突变,犬类和人类热点突变的直系同源。一个常见的同义词变体,BRAFT586T,在23%(47/196)的肿瘤中可见。怀疑该变体是单核苷酸多态性。BRAF在常见的猫科动物肿瘤或在人类和犬类癌症中经常携带BRAF突变的肿瘤类型中并不经常突变。正如在犬癌基因组学中所看到的,猫肿瘤中的突变谱可能与人类肿瘤学中的组织学等同物不平行。