Fibroblast Growth Factor Receptor 3 (FGFR3)–Analyses of the S249C Mutation and Protein Expression in Primary Cervical Carcinomas

Haiyan Dai, R. Holm, G. Kristensen, V. Abeler, A. Børresen-Dale, Å. Helland
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引用次数: 10

Abstract

Fibroblast growth factor receptor 3 (FGFR3) seems to play an inhibitory role in bone development, as activating mutations in the gene underlie disorders such as achondroplasia and thanatophoric dysplasia. Findings from multiple myeloma (MM) indicate that FGFR3 also can act as an oncogene, and mutation of codon 249 in the fibroblast growth factor receptor 3 (FGFR3) gene was recently detected in 3/12 primary cervical carcinomas. We have analysed 91 cervical carcinomas for this specific S249C mutation using amplification created restriction site methodology (ACRS), and detected no mutations. Immunohistochemistry was performed on 73 of the tumours. Reduced protein staining was seen in 43 (58.8%) samples. Six of the tumours (8.2%) revealed increased protein staining compared with normal cervical tissue. These patients had a better prognosis than those with reduced or normal levels, although not statistically significant. This report weakens the hypothesis of FGFR3 as an oncogene of importance in cervical carcinomas.
成纤维细胞生长因子受体3 (FGFR3) -原发性宫颈癌中S249C突变和蛋白表达分析
成纤维细胞生长因子受体3 (FGFR3)似乎在骨骼发育中起抑制作用,因为该基因的激活突变是软骨发育不全和嗜盐性发育不良等疾病的基础。多发性骨髓瘤(MM)的研究结果表明,FGFR3也可以作为致癌基因,最近在3/12的原发性宫颈癌中检测到成纤维细胞生长因子受体3 (FGFR3)基因密码子249的突变。我们使用扩增限制性内切位点方法(ACRS)分析了91例宫颈癌中这种特定的S249C突变,未检测到突变。73例肿瘤行免疫组化处理。43例(58.8%)蛋白染色降低。与正常宫颈组织相比,6例肿瘤(8.2%)显示蛋白染色增加。这些患者的预后比低水平或正常水平的患者好,尽管没有统计学意义。该报告削弱了FGFR3作为宫颈癌重要致癌基因的假设。
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