Wooster Richard, Futreal Andrew P, Stratton Michael R
Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
Methods Enzymol. 2006;407:218-24. doi: 10.1016/S0076-6879(05)07018-7.
Cancers arise because of the accumulation of mutations in critical genes that alter normal programs of cell proliferation, differentiation, and death. The RAS-RAF-MEK-ERK-MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in approximately 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. ARAF and c-RAF are infrequently mutated in human cancer. However, BRAF is mutated in a wide range of human cancers. Most mutations are within the kinase domain, with a single amino acid substitution (V600E) accounting for most mutations.
癌症的发生是由于关键基因中突变的积累，这些突变改变了细胞增殖、分化和死亡的正常程序。RAS-RAF-MEK-ERK-MAP激酶途径介导细胞对生长信号的反应。在大约15%的人类癌症中，RAS突变为致癌形式。三个RAF基因编码由结合RAS调节的细胞质丝氨酸/苏氨酸激酶。ARAF和c-RAF在人类癌症中很少发生突变。然而，BRAF在多种人类癌症中发生突变。大多数突变发生在激酶结构域内，单个氨基酸取代（V600E）占大多数突变。
