Kuroki Kei, Hoang Christine Tran, Rogic Anita M, Rindt Hans, Simenson Angelynn, Noall Lucie G, Bryan Jeffrey N, Johnson Gayle C, Chu Shirley
Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USA.
Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USA.
Vet Comp Oncol. 2024 Sep;22(3):452-456. doi: 10.1111/vco.12997. Epub 2024 Jul 17.
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 BRAF 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 BRAF 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 BRAF mutation, orthologous to the canine and human hotspot mutations. A common synonymous variant, BRAF, 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.
BRAF是多种RAF蛋白之一，负责激活参与细胞生长、分化和存活的MAPK细胞信号级联反应。已确定外显子15中的一个热点BRAF突变是100%毛细胞白血病、50%-60%人类黑色素瘤、30%-50%人类甲状腺癌和10%-20%人类结直肠癌的驱动因素。在犬膀胱移行细胞癌和前列腺腺癌中，分别有67%和80%出现了直系同源BRAF突变。由于兽医癌症和人类癌症利用相似的途径，且BRAF在物种间高度保守，因此BRAF有望成为猫科动物癌症的驱动因素。开发了引物以扩增猫科动物BRAF的外显子15。分析了196个猫科动物肿瘤。对211bp的PCR扩增子进行了桑格测序。在一个肿瘤（皮肤黑色素瘤）中发现了BRAF突变。该突变是一种BRAF突变，与犬类和人类的热点突变直系同源。在23%（47/196）的肿瘤中发现了一个常见的同义变体BRAF。该变体被怀疑是一个单核苷酸多态性。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发生突变。正如在犬类癌症基因组学中所见，猫科动物肿瘤的突变谱可能与人类肿瘤学中的组织学等效物不一致。
