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肺腺癌中表皮生长因子受体和KRAS突变:黎巴嫩人群的回顾性研究

Epidermal growth factor receptor and KRAS mutations in lung adenocarcinoma: a retrospective study of the Lebanese population.

作者信息

Fakhruddin Najla, Mahfouz Rami, Farhat Fadi, Tfayli Arafat, Abdelkhalik Rabab, Jabbour Mark, Yehia Lamis, Mahfoud Ziyad, Zaatari Ghazi

机构信息

Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon.

Department of Hematology-Oncology, Hammoud Hospital University Medical Center, Sidon, Lebanon.

出版信息

Oncol Rep. 2014 Nov;32(5):2223-9. doi: 10.3892/or.2014.3406. Epub 2014 Aug 14.

Abstract

Molecular genetic analysis of epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) mutations in lung adenocarcinoma has become an integral part of lung cancer diagnosis and treatment; however, their prevalence varies with ethnicity. Little is know concerning their prevalence in Arab populations. In the present study, mutational analysis for EGFR and KRAS was performed on two cohorts of the Lebanese population. Lung adenocarcinoma cases (106) underwent mutational analysis for KRAS in exon 2, codon 12 and 13 and exon 3 codon 61 by reverse hybridization using the KRAS 12/13/61 StripAssay®. Subsequently, cases with no KRAS mutations underwent EGFR mutational analysis using the EGFR RGQ polymerase chain reaction (PCR) kits for real‑time PCR on the Rotor‑Gene Q 5-plex HRM. KRAS mutations were detected in 37.7% of 106 lung adenocarcinomas; 85% had a G>T substitution in codon 12 and 13 of exon 2, and 8.5% had EGFR mutations with exon 19 deletions (88.9%) and one case with L858R substitution in exon 21. EGFR mutations were significantly correlated with females, non-smokers and well differentiation of the tumor. This is the first study in an Arab population that reports the prevalence of both EGFR and KRAS gene mutations in lung adenocarcinoma using very sensitive mutational analysis techniques. Therefore, EGFR reflex testing should be implemented in the management of lung adenocarcinomas, while KRAS testing must await the identification of effective targeted therapy.

摘要

对肺腺癌中表皮生长因子受体(EGFR)和 Kirsten 大鼠肉瘤病毒癌基因(KRAS)突变进行分子遗传学分析已成为肺癌诊断和治疗不可或缺的一部分;然而,它们的患病率因种族而异。关于它们在阿拉伯人群中的患病率知之甚少。在本研究中,对两组黎巴嫩人群进行了 EGFR 和 KRAS 的突变分析。106 例肺腺癌病例通过使用 KRAS 12/13/61 StripAssay® 反向杂交技术,对第 2 外显子密码子 12 和 13 以及第 3 外显子密码子 61 进行 KRAS 突变分析。随后,对无 KRAS 突变的病例使用 EGFR RGQ 聚合酶链反应(PCR)试剂盒在 Rotor-Gene Q 5-plex HRM 上进行实时 PCR 检测 EGFR 突变。在 106 例肺腺癌中,37.7%检测到 KRAS 突变;85%在第 2 外显子密码子 12 和 13 处发生 G>T 替换,8.5%发生 EGFR 突变,其中 19 外显子缺失占 88.9%,1 例在第 21 外显子发生 L858R 替换。EGFR 突变与女性、非吸烟者以及肿瘤的高分化显著相关。这是阿拉伯人群中第一项使用非常敏感的突变分析技术报告肺腺癌中 EGFR 和 KRAS 基因突变患病率的研究。因此,在肺腺癌的管理中应实施 EGFR 反射检测,而 KRAS 检测必须等待有效靶向治疗的确定。

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