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Clinicopathologic features of non-small-cell lung cancer with EML4-ALK fusion geneTsuyoshi Takahashi et al. Ann Surg Oncol. 2010 Mar.
doi: 10.1245/s10434-009-0808-7. Authors Tsuyoshi Takahashi 1 , Makoto Sonobe, Masashi Kobayashi, Akihiko Yoshizawa, Toshi Menju, Ei Nakayama, Nobuya Mino, Shotaro Iwakiri, Kiyoshi Sato, Ryo Miyahara, Kenichi Okubo, Toshiaki Manabe, Hiroshi Date AffiliationItem in Clipboard
AbstractBackground: A fusion gene between echinoderm microtubule-associated protein-like 4 (EML4) and the anaplastic lymphoma kinase (ALK) has recently been identified in nonsmall-cell lung cancers (NSCLCs). We screened for EML4-ALK fusion genes and examined the clinicopathological and genetic characteristics of fusion-harboring NSCLC tumors.
Methods: 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.
Results: 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.
Conclusions: 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.
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