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西班牙头颈癌患者中表皮生长因子受体(EGFR)激酶结构域无激活突变。

Absence of activating mutations in the EGFR kinase domain in Spanish head and neck cancer patients.

作者信息

Lemos-González Y, Páez de la Cadena M, Rodríguez-Berrocal F J, Rodríguez-Piñeiro A M, Pallas E, Valverde D

机构信息

Department of Biochemistry, Genetics and Immunology, University of Vigo, Vigo, Spain.

出版信息

Tumour Biol. 2007;28(5):273-9. doi: 10.1159/000110425. Epub 2007 Oct 26.

Abstract

The discovery of kinase domain mutations in the epidermal growth factor receptor gene (EGFR) in never-smoker patients, associated with an increased sensitivity to tyrosine kinase inhibitors (TKIs) such as gefitinib or erlotinib, has been one of the most relevant findings ever in non-small cell lung carcinomas (NSCLC). Since treatment with TKIs has furthermore shown a clinical benefit in head and neck squamous cell carcinoma (HNSCC) patients, we hypothesized that these mutations could also be present in this neoplasia. Current studies looking for EGFR mutations in HNSCC are limited and results are still controversial. In this work, we screened for EGFR tyrosine kinase mutations in tumour DNA obtained from 31 Spanish patients with HNSCC by PCR-single-strand conformational polymorphism analysis. None of the patients displayed a somatic EGFR mutation, previously described in NSCLC, but other DNA sequence variations were found in 9 of 31 HNSCC patients. Accordingly, activating EGFR mutations in HNSCC patients seem to be a rare event in Spanish patients, suggesting that there is little room for the administration of TKIs in HNSCC based on the presence of these mutations. Additional investigations about EGFR amplification are indicated to establish a potential relationship between EGFR overexpression and the response to anti-EGFR therapies.

摘要

在不吸烟的非小细胞肺癌(NSCLC)患者中发现表皮生长因子受体基因(EGFR)激酶结构域突变与对吉非替尼或厄洛替尼等酪氨酸激酶抑制剂(TKIs)的敏感性增加相关,这是NSCLC领域最重大的发现之一。由于TKIs治疗在头颈部鳞状细胞癌(HNSCC)患者中也显示出临床益处,我们推测这些突变在该肿瘤中也可能存在。目前针对HNSCC中EGFR突变的研究有限,结果仍存在争议。在这项研究中,我们通过PCR-单链构象多态性分析,对31例西班牙HNSCC患者肿瘤DNA中的EGFR酪氨酸激酶突变进行了筛查。没有患者出现NSCLC中先前描述的体细胞EGFR突变,但在31例HNSCC患者中有9例发现了其他DNA序列变异。因此,在西班牙患者中,HNSCC患者激活型EGFR突变似乎是罕见事件,这表明基于这些突变给予TKIs治疗HNSCC的空间很小。需要对EGFR扩增进行更多研究,以确定EGFR过表达与抗EGFR治疗反应之间的潜在关系。

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