Recurrent FGFR 1 amplification and high FGFR1 protein expression in oral squamous cell carcinoma (OSCC)
Recurrent FGFR 1 amplification and high FGFR1 protein expression in oral squamous cell carcinoma (OSCC)
复制标题
DOI：
10.1016/j.oraloncology.2006.01.005
复制
发表时间：
2007-01-01
期刊：
影响因子：
4.8
通讯作者：
Joos, Stefan
中科院分区：
文献类型：
--
作者：
Freier, Kolja;Schwaenen, Carsten;Joos, Stefan
染色体畸变对口腔鳞状细胞癌（OSCC）的发生和发展有影响，但涉及OSCC发病机制的单个基因的描述很少。为了阐明口腔癌发生的分子机制，我们采用基于阵列的比较基因组杂交技术对一组原发性口腔鳞癌进行了基因不平衡的筛查。为此，使用了含有812个基因组靶标的DNA阵列，所述基因组靶标包括致癌基因、肿瘤抑制基因和在人类肿瘤中经常改变的染色体区域。最常见的畸变是MYC、EGFR、CCND 1和PIK 3CA的扩增，而缺失影响TRAILR 1和ATM。此外，在两种情况下，检测到成纤维细胞生长因子受体1（FGFR 1）基因座的明显高水平扩增。对OSCC组织芯片切片的详细FISH分析显示FGFR 1的扩增率为17.4%（16/92）。此外，通过免疫组织化学对包含178例OSCC的TMA进行FGFR 1蛋白分析，发现FGFR 1在早期t期和UICC期肿瘤中表达较高（T1/2 vs. T3/4：p = 0.002; SI-II vs. S III-IV：p = 0.048）。我们的研究结果表明，FGFR 1表达的增加有助于口腔癌的早期发展阶段。(c)2006爱思唯尔有限公司保留所有权利。
Chromosomal aberrations are known to have an impact on the initiation and progression of oral squamous cell carcinoma (OSCC), but individual genes involved in OSCC pathogenesis are poorly described. To elucidate the molecular events underlying oral carcinogenesis, a set of primary OSCC were screened for distinct genetic imbalances by means of array-based comparative genomic hybridisation. For this, a DNA array was used containing 812 genomic targets including oncogenes, tumour-suppressor genes and chromosomal regions frequently altered in human neoplasms. The most frequent aberrations were amplification of MYC, EGFR, CCND1 and PIK3CA, whereas deletions affected TRAILR1 and ATM. Furthermore, a distinct high-level amplification of the fibroblast growth factor receptor 1 (FGFR1) locus was detected in two cases. Detailed FISH analysis on OSCC tissue microarray sections revealed amplification prevalence for FGFR1 of 17.4% (16/92). Furthermore, FGFR1 protein analysis by immunohistochemistry on a TMA containing 178 OSCC found a high FGFR1 expression in tumours of early t-stadiumand UICC stage (T1/2 vs. T3/4: p = 0.002; SI-II vs. S III-IV: p = 0.048). Our results indicate that an increase in FGFR1 expression contributes to oral carcinogenesis at an early stage of development. (c) 2006 Elsevier Ltd. All rights reserved.