Increased ALK gene copy number and amplification are frequent in non-small cell lung cancer

Marta Salido, Lara Pijuan, Luz Martínez-Avilés, Ana B. Galván, Israel Cañadas, Ana Rovira, Montserrat Zanui, Alejandro Martínez, Raquel Longarón, Francisco Sole, Sergio Serrano, Beatriz Bellosillo, Murry W. Wynes, Joan Albanell, Fred R. Hirsch, Edurne Arriola

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124 Citations (Scopus)

Abstract

INTRODUCTION: Translocation of the anaplastic lymphoma kinase (ALK) gene is involved in the tumorigenesis of a subset of non-small cell lung carcinomas (NSCLCs) and identifies patients sensitive to ALK inhibitors. ALK copy number changes and amplification, which plays an oncogenic role in tumors such as neuroblastoma, are poorly characterized in NSCLC. We aimed to study the prevalence of ALK copy number changes and their correlation to ALK protein expression, epidermal growth factor receptor (EGFR) status, and clinicopathological data in patients with NSCLC. METHODS: ALK status was evaluated by fluorescence in situ hybridization (FISH). Specimens with ALK translocation were studied for echinoderm microtubule-associated protein-like 4 (EML4), KIF5B, and TFG status. ALK expression was assessed by immunohistochemistry. EGFR gene and protein status were evaluated in adenocarcinomas. Survival analysis was performed. RESULTS: One hundred seven NSCLC cases were evaluated. There were two cases of EML4-ALK translocation and one with an atypical translocation of ALK. Both cases of EML4-ALK translocation had ALK protein expression, whereas in the rest, ALK was undetected. Eleven cases (10%) exhibited ALK amplification and 68 (63%) copy number gains. There was an association between ALK amplification and EGFR FISH positivity (p < 0.0001) but not with prognosis. In conclusion, EML4-ALK translocation is a rare event in NSCLC. CONCLUSION: The study reveals a significant frequency of ALK amplification and its association with EGFR FISH positivity in lung adenocarcinomas. Based on these findings, a potential role of ALK amplification in the response to ALK inhibitors alone or combined with EGFR inhibitors in NSCLC merits further studies. Copyright © 2010 by the international Association fot the Study of lung Cancer.
Original languageEnglish
Pages (from-to)21-27
JournalJournal of Thoracic Oncology
Volume6
Issue number1
DOIs
Publication statusPublished - 1 Jan 2011

Keywords

  • ALK
  • Amplification
  • Non-small cell lung cancer
  • Polysomy
  • Translocation

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