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Annals of Surgical Oncology

, Volume 17, Issue 3, pp 889–897 | Cite as

Clinicopathologic Features of Non-Small-Cell Lung Cancer with EML4ALK Fusion Gene

  • Tsuyoshi Takahashi
  • Makoto SonobeEmail author
  • Masashi Kobayashi
  • Akihiko Yoshizawa
  • Toshi Menju
  • Ei Nakayama
  • Nobuya Mino
  • Shotaro Iwakiri
  • Kiyoshi Sato
  • Ryo Miyahara
  • Kenichi Okubo
  • Toshiaki Manabe
  • Hiroshi Date
Translational Research and Biomarkers

Abstract

Background

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.

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.

Keywords

Epidermal Growth Factor Receptor Gefitinib Erlotinib Anaplastic Lymphoma Kinase Pulmonary Resection 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgment

We thank Ms. Seiko Sakai for excellent secretarial assistance. This project was not supported by any outside funds.

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Copyright information

© Society of Surgical Oncology 2009

Authors and Affiliations

  • Tsuyoshi Takahashi
    • 1
  • Makoto Sonobe
    • 1
    Email author
  • Masashi Kobayashi
    • 1
  • Akihiko Yoshizawa
    • 2
  • Toshi Menju
    • 1
  • Ei Nakayama
    • 1
  • Nobuya Mino
    • 1
  • Shotaro Iwakiri
    • 1
  • Kiyoshi Sato
    • 1
  • Ryo Miyahara
    • 1
  • Kenichi Okubo
    • 1
  • Toshiaki Manabe
    • 2
  • Hiroshi Date
    • 1
  1. 1.Department of Thoracic Surgery, Faculty of MedicineKyoto UniversityKyotoJapan
  2. 2.Diagnostic Pathology, Faculty of MedicineKyoto UniversityKyotoJapan

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