| Summary: | <p>Abstract</p> <p>Background</p> <p>Anaplastic lymphoma receptor tyrosine kinase (<it>ALK</it>) gene rearrangements have been reported in 2-13% of patients with non-small cell lung cancer (NSCLC). Patients with <it>ALK</it> rearrangements do not respond to EGFR-specific tyrosine kinase inhibitors (TKIs); however, they do benefit from small molecule inhibitors targeting ALK.</p> <p>Results</p> <p>In this study, fluorescence in situ hybridization (FISH) using a break-apart probe for the <it>ALK</it> gene was performed on formalin fixed paraffin-embedded tissue to determine the incidence of <it>ALK</it> rearrangements and hybridization patterns in a large unselected cohort of 1387 patients with a referred diagnosis of non-small cell lung cancer (1011 of these patients had a histologic diagnosis of adenocarcinoma). The abnormal FISH signal patterns varied from a single split signal to complex patterns. Among 49 abnormal samples (49/1387, 3.5%), 32 had 1 to 3 split signals. Fifteen samples had deletions of the green 5<sup>′</sup> end of the <it>ALK</it> signal, and 1 of these 15 samples showed amplification of the orange 3<sup>′</sup> end of the <it>ALK</it> signal. Two patients showed a deletion of the 3<sup>′</sup><it>ALK</it> signal. Thirty eight of these 49 samples (38/1011, 3.7%) were among the 1011 patients with confirmed adenocarcinoma. Five of 8 patients with <it>ALK</it> rearrangements detected by FISH were confirmed to have <it>EML4-ALK</it> fusions by multiplex RT-PCR. Among the 45 <it>ALK</it>-rearranged samples tested, only 1 <it>EGFR</it> mutation (T790M) was detected. Two <it>KRAS</it> mutations were detected among 24 <it>ALK</it>-rearranged samples tested.</p> <p>Conclusions</p> <p>In a large unselected series, the frequency of <it>ALK</it> gene rearrangement detected by FISH was approximately 3.5% of lung carcinoma, and 3.7% of patients with lung adenocarcinoma, with variant signal patterns frequently detected. Rare cases with coexisting <it>KRAS</it> and <it>EGFR</it> mutations were seen.</p>
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