EML4-ALK fusion lung cancer: a rare acquired event

Sven Perner, PATRICK L WAGNER, Francesca Demichelis, Rohit Mehra, Christopher J LaFargue, Benjamin J Moss, Stefanie Arbogast, Alex Soltermann, Walter Weder, Thomas J Giordano, David G Beer, David S. Rickman, Arul M Chinnaiyan, Holger Moch and Mark A Rubin

Year 2008, Volume 10, Issue 3

Abstract

A recurrent gene fusion between EML4 and ALK in 6.7% of non-small cell lung cancers (NSCLC) and TTF1 high-level amplifications in 12% of adenocarcinomas of the lung was independently reported recently. Since the EML4-ALK fusion was only shown by a RT-PCR approach, we developed in-situ FISH assays to interrogate over 600 non-small cell lung cancers using break-apart probes for EML4 and ALK. We found that EML4-ALK fusions occur in less than 3% of NSCLC samples and that also EML4 and/or ALK amplifications occur. We also observed that in most cases in which an EML4/ALK alteration is detected not all of the tumor cells harbor the lesion. By using a detailed multi-FISH probe assay and RT-PCR, we have evidence that other, more common mechanisms besides gene inversion exist including the possibility of other fusion partners for ALK and EML4. Furthermore, we confirmed the TTF1 high-level amplification in a significant subset of NSCLC, and found this amplification to be mutually exclusive to ALK and EML4 rearrangements.

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