Identification of <i>ALK</i> Gene Alterations in Urothelial Carcinoma

<div><p>Background</p><p>Anaplastic lymphoma kinase (<i>ALK</i>) genomic alterations have emerged as a potent predictor of benefit from treatment with <i>ALK</i> inhibitors in several cancers. Currently, there is no information about <i>ALK</i> gene alterations in urothelial carcinoma (UC) and its correlation with clinical or pathologic features and outcome.</p><p>Methods</p><p>Samples from patients with advanced UC and correlative clinical data were collected. Genomic imbalances were investigated by array comparative genomic hybridization (aCGH). <i>ALK</i> gene status was evaluated by fluorescence <i>in situ</i> hybridization (FISH). <i>ALK</i> expression was assessed by immunohistochemistry (IHC) and high-throughput mutation analysis with Oncomap 3 platform. Next generation sequencing was performed using Illumina Genome Analyzer IIx, and Illumina HiSeq 2000 in the FISH positive case.</p><p>Results</p><p>70 of 96 patients had tissue available for all the tests performed. Arm level copy number gains at chromosome 2 were identified in 17 (24%) patients. Minor copy number alterations (CNAs) in the proximity of <i>ALK</i> locus were found in 3 patients by aCGH. By FISH analysis, one of these samples had a deletion of the <i>5′ALK</i>. Whole genome next generation sequencing was inconclusive to confirm the deletion at the level of the <i>ALK</i> gene at the coverage level used. We did not observe an association between <i>ALK</i> CNA and overall survival, ECOG PS, or development of visceral disease.</p><p>Conclusions</p><p><i>ALK</i> genomic alterations are rare and probably without prognostic implications in UC. The potential for testing <i>ALK</i> inhibitors in UC merits further investigation but might be restricted to the identification of an enriched population.</p>