EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib
EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib
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DOI：
10.1073/pnas.0405220101
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发表时间：
2004-09-07
影响因子：
11.1
通讯作者：
Varmus, H
中科院分区：
文献类型：
--
作者：
Pao, W;Miller, V;Varmus, H
据报道，表皮生长因子受体（EGFR）基因酪氨酸激酶（TK）结构域的体细胞突变与肺癌对激酶抑制剂吉非替尼（易瑞沙）的敏感性相关。框内缺失发生在外显子19，而点突变经常发生在密码子858（外显子21）。我们通过对EGFR TK结构域的测序发现，10例吉非替尼敏感性肿瘤中有7例具有相似类型的改变;在8例吉非替尼难治性肿瘤中未发现突变（P = 0.004）。对厄洛替尼（特罗凯）敏感的7个肿瘤中有5个有类似的体细胞突变，而10个厄洛替尼难治性肿瘤中没有一个有类似的体细胞突变（P = 0.003）。因为大多数突变阳性的肿瘤是腺癌，来自吸烟的患者，
Somatic mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene are reportedly associated with sensitivity of lung cancers to gefitinib (Iressa), kinase inhibitor. in-frame deletions occur in exon 19, whereas point mutations occur frequently in codon 858 (exon 21). We found from sequencing the EGFR TK domain that 7 of 10 gefitinib-sensitive tumors had similar types of alterations; no mutations were found in eight gefitinib-refractory tumors (P = 0.004). Five of seven tumors sensitive to erlotinib (Tarceva), a related kinase inhibitor for which the clinically relevant target is undocumented, had analogous somatic mutations, as opposed to none of 10 erlotinib-refractory tumors (P = 0.003). Because most mutation-positive tumors were adenocarcinomas from patients who smoked