Clinicopathologic Features of Non-Small-Cell Lung Cancer with EML4-ALK Fusion Gene
Clinicopathologic Features of Non-Small-Cell Lung Cancer with EML4-ALK Fusion Gene
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DOI：
10.1245/s10434-009-0808-7
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发表时间：
2010-03-01
影响因子：
3.7
通讯作者：
Date, Hiroshi
中科院分区：
文献类型：
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作者：
Takahashi, Tsuyoshi;Sonobe, Makoto;Date, Hiroshi
棘皮动物微管相关蛋白样4（EML 4）和间变性淋巴瘤激酶（ALK）之间的融合基因最近在非小细胞肺癌（NSCLC）中被发现。我们对2001年5月至2005年7月期间在我院接受手术切除的313例NSCLC患者进行了EML 4-ALK融合基因筛查，并检查了融合型NSCLC肿瘤的临床病理学和遗传学特征。我们用逆转录聚合酶链反应（RT-PCR）方法筛选融合基因，并用直接测序法证实结果。我们还检测了表皮生长因子受体（EGFR）、KRAS和ERBB 2基因的突变，检测到5个EML 4-ALK融合基因（4个来自111个女性样本，1个来自202个男性样本;总体为1.6%）。所有五个基因都在腺癌中发现，占211个腺癌样本的2.4%。一个EML 4-ALK融合体是变体1，两个是变体3。此外，我们还发现了两个新的融合变体。融合阳性肿瘤患者为非吸烟者或轻度吸烟者。在211例腺癌中，分别在105例、29例和7例肿瘤中检测到EGFR、KRAS和ERBB 2突变。有趣的是，所有融合阳性的NSCLC均未发现这些基因的突变。EML 4-ALK融合基因主要见于腺癌、女性或非吸烟人群。此外，EML 4-ALK融合与EGFR、KRAS和ERBB 2基因突变相互排斥。
A fusion gene between echinoderm microtubule-associated protein-like 4 (EML4) and the anaplastic lymphoma kinase (ALK) has recently been identified in non-small-cell lung cancers (NSCLCs). We screened for EML4-ALK fusion genes and examined the clinicopathological and genetic characteristics of fusion-harboring NSCLC tumors.We examined 313 NSCLC samples from patients who underwent resection at our hospital between May 2001 and July 2005. We screened for the fusion genes using reverse-transcription polymerase chain reaction (RT-PCR) assay and confirmed the results with direct sequencing. We also examined mutations in the epidermal growth factor receptor (EGFR), KRAS, and ERBB2 genes.Five EML4-ALK fusion genes were detected (four from 111 female samples and one from 202 male samples; 1.6% overall). All five genes were found in adenocarcinomas and accounted for 2.4% of the 211 adenocarcinoma samples. One EML4-ALK fusion was variant 1, and two were variant 3. In addition, we also found two new fusion variants. Patients with fusion-positive tumors were nonsmokers or light smokers. Among the 211 adenocarcinomas, mutations in EGFR, KRAS, and ERBB2 were detected in 105, 29, and 7 tumors, respectively. Interestingly, all of the fusion-positive NSCLCs had no mutations within these genes.EML4-ALK fusion genes were observed predominantly in adenocarcinomas, in female or nonsmoking populations. Additionally, the EML4-ALK fusions were mutually exclusive with mutations in the EGFR, KRAS, and ERBB2 genes.