TP53, EGFR, and KRAS mutations in relation to VHL inactivation and lifestyle risk factors in renal-cell carcinoma from central and eastern Europe.
TP53, EGFR, and KRAS mutations in relation to VHL inactivation and lifestyle risk factors in renal-cell carcinoma from central and eastern Europe.
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DOI：
10.1016/j.canlet.2009.11.024
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发表时间：
2010-07
期刊：
影响因子：
9.7
通讯作者：
Katarzyna Szymańska;L. E. Moore;Nathanial Rothman;Wong-Ho Chow;Frederic M. Waldman;Erich B. Jaeger;T. Waterboer;L. Foretova;M. Navratilova;V. Janout;H. Kollárová;D. Zaridze;Vsevolod Matveev;D. Mates;N. szeszenia-Dabrowska;I. Holcatova;V. Bencko;F. Calvez-Kelm;S. Villar;M. Pawlita;Paolo Boffetta;Pierre Hainaut;P. Brennan
中科院分区：
文献类型：
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作者：
Katarzyna Szymańska;L. E. Moore;Nathanial Rothman;Wong-Ho Chow;Frederic M. Waldman;Erich B. Jaeger;T. Waterboer;L. Foretova;M. Navratilova;V. Janout;H. Kollárová;D. Zaridze;Vsevolod Matveev;D. Mates;N. szeszenia-Dabrowska;I. Holcatova;V. Bencko;F. Calvez-Kelm;S. Villar;M. Pawlita;Paolo Boffetta;Pierre Hainaut;P. Brennan
肾细胞癌(RCC)在中欧和东欧很常见，其原因尚不清楚。分子机制，除了VHL，还没有太多的研究。我们分析了来自一项多中心病例对照研究的361例RCC(334例透明细胞癌)和50例肿瘤的EGFR(外显子18-21)或KRAS(密码子12)突变与VHL状态的关系。在4%的透明细胞病例中检测到TP53突变，与VHL突变无关。在非透明细胞癌中，在11%的VHL野生型肿瘤中检测到它们，在具有VHL功能突变的肿瘤中检测到0%。未发现EGFR和KRAS基因突变。我们的结论是，即使在没有VHL失活的情况下，TP53、KRAS或EGFR的突变也不是肾癌发生的主要原因。在透明细胞癌和其他肾癌中，与VHL状态相关的TP53突变的发生率可能不同。
Renal-cell carcinomas (RCC) are frequent in central and eastern Europe and the reasons remain unclear. Molecular mechanisms, except for VHL, have not been much investigated. We analysed 361 RCCs (334 clear-cell carcinomas) from a multi-centre case-control study for mutations in TP53 (exons 5–9 in the whole series and exons 4 and 10 in a pilot subset of 60 tumours) and a pilot 50 tumours for mutations in EGFR (exons 18–21) or KRAS (codon 12) in relation to VHL status. TP53 mutations were detected in 4% of clear-cell cases, independently of VHL mutations. In non-clear-cell carcinomas, they were detected in 11% of VHL-wild-type tumours and in 0% of tumours with VHL functional mutations. No mutations were found in EGFR or KRAS. We conclude that mutations in TP53, KRAS, or EGFR are not major contributors to the RCC development even in the absence of VHL inactivation. The prevalence of TP53 mutations in relation to VHL status may differ between clear-cell and other renal carcinomas.