Katoh Masaru
Genetics and Cell Biology Section, National Cancer Center Research Institute, Chuo-ward, Tokyo 104-0045, Japan.
Int J Oncol. 2008 Aug;33(2):233-7.
FGFR2 gene encodes FGFR2b in epithelial cells, and FGFR2c in mesenchymal cells. FGFR2b is a high affinity receptor for FGF1, FGF3, FGF7, FGF10 and FGF22, while FGFR2c for FGF1, FGF2, FGF4, FGF6, FGF9, FGF16 and FGF20. Here genomics and genetics of FGFR2, and therapeutics targeted to FGFR2 will be reviewed. Single nucleotide polymorphisms (SNPs) of FGFR2 are associated with increased risk of breast cancer. Gene amplification or missense mutation of FGFR2 occurs in gastric cancer, lung cancer, breast cancer, ovarian cancer, and endometrial cancer. Genetic alterations of FGFR2 induce aberrant FGFR2 signaling activation due to release of FGFR2 from autoinhibition, or creation of FGF signaling autocrine loop. Class switch of FGFR2b to FGFR2c is associated with more malignant phenotype. FGF and canonical WNT signals synergize during mammary carcinogenesis, but counteract during osteogenesis and adipogenesis. Among PD173074, SU5402, and AZD2171 functioning as FGFR inhibitors, AZD2171 is the most promising anti-cancer drug. Cancer genomics and genetics are utilized to predict cancer-driving pathway for therapeutic optimization. FGFR2ome is defined as a complete data set of SNP, copy number variation (CNV), missense mutation, gene amplification, and predominant isoform of FGFR2. FGFR2ome analyses in patients with several tumor types among various populations should be carried out to establish integrative database of FGFR2 for the rational clinical application of FGFR2-targeted cancer therapy.
FGFR2基因在上皮细胞中编码FGFR2b，在间充质细胞中编码FGFR2c。FGFR2b是FGF1、FGF3、FGF7、FGF10和FGF22的高亲和力受体，而FGFR2c是FGF1、FGF2、FGF4、FGF6、FGF9、FGF16和FGF20的受体。在此，将对FGFR2的基因组学和遗传学以及针对FGFR2的治疗方法进行综述。FGFR2的单核苷酸多态性（SNP）与乳腺癌风险增加相关。FGFR2的基因扩增或错义突变发生在胃癌、肺癌、乳腺癌、卵巢癌和子宫内膜癌中。FGFR2的基因改变由于FGFR2从自身抑制中释放或FGF信号自分泌环的形成而诱导异常的FGFR2信号激活。FGFR2b向FGFR2c的类别转换与更恶性的表型相关。FGF和经典WNT信号在乳腺癌发生过程中协同作用，但在骨生成和脂肪生成过程中相互拮抗。在作为FGFR抑制剂发挥作用的PD173074、SU5402和AZD2171中，AZD2171是最有前景的抗癌药物。癌症基因组学和遗传学被用于预测癌症驱动途径以优化治疗。FGFR2ome被定义为FGFR2的SNP、拷贝数变异（CNV）、错义突变、基因扩增和主要异构体的完整数据集。应在不同人群中的几种肿瘤类型患者中进行FGFR2ome分析，以建立FGFR2的综合数据库，用于FGFR2靶向癌症治疗的合理临床应用。
