BRAF基因突变的机制及在不同肿瘤中的临床意义

Mechanism of BRAF Gene Mutation and Its Clinical Significance in Different Tumors

鼠类肉瘤病毒癌基因同源物B1(BRAF)基因是促分裂原活化的蛋白激酶(MAPK)信号调节通路中的一个关键角色,这种突变异常可激活MAPK激酶/胞外信号调节激酶(ERK)信号通路,从而参与细胞的增殖、分化和凋亡过程。BRAF突变的意义源于其预后价值,及时的干预和对因治疗能够为患者带来更多的临床获益。在分子靶向治疗时代,BRAF突变已被确定为许多癌症中的靶向致癌突变,并与肿瘤的临床病理特征、预后以及治疗密切相关,尤其是甲状腺乳头状癌。但BRAF与MAPK/ERK通路及其下游相关信号通路的具体分子作用机制仍需要进一步研究。

The v-raf murine sarcoma viral oncogene homolog B1(BRAF)gene is a key player in the mitogen-activated protein kinase(MAPK)signal-modulating pathway,and its abnormal mutation activates the MAPK kinase/extracellular signal-regulated kinase(ERK)signaling pathway and is thus involved in cell proliferation,differentiation and apoptosis.The significance of BRAF mutations stems from their prognostic value,and timely intervention and treatment can bring more clinical benefits to the patients.In the era of molecularly targeted therapy,BRAF mutations have been identified as targeted oncogenic mutations in many cancers and are closely related to the clinicopathological characteristics,prognosis and treatment of tumors,especially thyroid papillary carcinoma.However,the specific molecular mechanism of action of BRAF and the MAPK/ERK pathway and its downstream related signaling pathways still needs further studies.