EGFR mutation status in Japanese lung cancer patients: Genotyping analysis using LightCycler
EGFR mutation status in Japanese lung cancer patients: Genotyping analysis using LightCycler
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DOI：
10.1158/1078-0432.ccr-04-1904
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发表时间：
2005-04-15
影响因子：
11.5
通讯作者：
Fujii, Y
中科院分区：
文献类型：
--
作者：
Sasaki, H;Endo, K;Fujii, Y
目的：最近，在大约 25% 的日本肺癌患者中发现了表皮生长因子受体 (EGFR) 基因的体细胞突变。据报道，这些 EGFR 突变与吉非替尼治疗的临床反应相关。然而，使用迄今为止描述的 PCR 方法进行 DNA 测序非常耗时，并且需要大量 DNA；因此，这种现有方法不适合常规的治疗前筛查计划。 实验设计：我们对日本肺癌患者的 EGFR 突变状态进行了基因分型，其中包括来自名古屋市立大学医院的 102 例手术治疗的肺癌病例和来自近畿中央胸科医疗中心的 16 例接受吉非替尼治疗的肺癌病例。使用突变特异性传感器和锚定探针，通过实时定量 PCR 分析是否存在三种常见 EGFR 突变。 结果：在外显子 21 中，102 名名古屋患者中的 8 名和来自近畿的 16 名患者中发现了 1 名 EGFR 突变（CTG -> CGG；L858R）。我们还检测到来自名古屋的 102 名患者中的 7 名（均为 1a 型缺失）和来自近畿的 16 名患者中的 4 名（1 名是 la 型，3 名是 1b 型）的外显子 19 缺失突变。在外显子 18 中，名古屋和近畿地区均发现了 G719S 突变的一个例子。 L858R突变与性别（女性与男性，P<0.0001）、Brinkman指数（600，P=0.001）、病理亚型（腺癌与非腺癌，P=0.007）以及肺癌的分化状态（良好与中度或较差，P=0.0439）显着相关，而缺失突变体则不然。 EGFR 基因状态，包括 EGFR 体细胞突变类型，与吉非替尼治疗的敏感性相关。例如，我们的一些对吉非替尼有反应的患者具有 L858R 或缺失型 la 突变。另一方面，我们的一名吉非替尼耐药患者存在 G719S 突变。结论：使用 LightCycler PCR 检测，EGFR L858R 突变状态可能与肺癌的性别、病理亚型和吉非替尼敏感性相关。然而，需要进一步的基因分型研究来证实EGFR突变对吉非替尼治疗肺癌的敏感性或耐药性的机制。
Purpose: Recently, somatic mutations of the epidermal growth factor receptor (EGFR) gene were found in similar to 25% of Japanese lung cancer patients. These EGFR mutations are reported to be correlated with clinical response to gefitinib therapy. However, DNA sequencing using the PCR methods described to date is time-consuming and requires significant quantities of DNA; thus, this existing approach is not suitable for a routine pretherapeutic screening program.Experimental Design: We have genotyped EGFR mutation status in Japanese lung cancer patients, including 102 surgically treated lung cancer cases from Nagoya City University Hospital and 16 gefitinib-treated lung cancer cases from Kinki-chuo Chest Medical Center. The presence or absence of three common EGFR mutations were analyzed by real-time quantitative PCR with mutation-specific sensor and anchor probes.Results: In exon 21, EGFR mutations (CTG -> CGG; L858R) were found from 8 of 102 patients from Nagoya and 1 of 16 from Kinki. We also detected the deletion mutations in exon 19 from 7 of 102 patients from Nagoya (all were deletion type 1a) and 4 of 16 patients from Kinki (one was type la and three were type 1b). In exon 18, one example of G719S mutation was found from both Nagoya and Kinki. The L858R mutation was significantly correlated with gender (women versus men, P < 0.0001), Brinkman index (600 , P = 0.001), pathologic subtypes (adenocarcinoma versus nonadenocarcinoma, P = 0.007), and differentiation status of the lung cancers (well versus moderately or poorly, P = 0.0439), whereas the deletion mutants were not. EGFR gene status, including the type of EGFR somatic mutation, was correlated with sensitivity to gefitinib therapy. For example, some of our gefitinib-responsive patients had L858R or deletion type la mutations. On the other hand, one of our gefitinib-resistant patients had a G719S mutation.Conclusions: Using the LightCycler PCR assay, the EGFR L858R mutation status might correlate with gender, pathologic subtypes, and gefitinib sensitivity of lung cancers. However, further genotyping studies are needed to confirm the mechanisms of EGFR mutations for the sensitivity or resistance of gefitinib therapy for the lung cancer.