Detection of known and novel ALK fusion transcripts in lung cancer patients using next-generation sequencing approaches

Julie A. Vendrell (1) , Sylvie Taviaux (1) , Beno\ⁱt Béganton (2, 3) , Sylvain Godreuil (1, 4) , Patricia Audran (3) , David Grand (5) , Estelle Clermont (6) , Isabelle Serre (1) , Vanessa Szablewski (1) , Peter Coopman (2, 3) , Julien Mazières (7) , Valérie Costes (1, 4) , Jean-Louis Pujol (1, 2) , Pierre Brousset (8) , Isabelle Rouquette (6) , Jérôme Solassol (9, 3, 2)

1 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
2 IRCM - U1194 Inserm - UM - Institut de Recherche en Cancérologie de Montpellier
3 ICM - UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle
4 Pathogénèse et contrôle des infections chroniques (PCCI)
5 CMW - Centre Max Weber
6 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
7 Service Pneumologie-Allergologie [CHU Toulouse]
8 CRCT - Centre de Recherches en Cancérologie de Toulouse
9 UM - Université de Montpellier

Rearrangements of the anaplastic lymphoma kinase (ALK) gene in non-small cell lung cancer (NSCLC) represent a novel molecular target in a small subset of tumors. Although ALK rearrangements are usually assessed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), molecular approaches have recently emerged as relevant alternatives in routine laboratories. Here, we evaluated the use of two different amplicon-based next-generation sequencing (NGS) methods (AmpliSeq and Archer\textregisteredFusionPlex\textregistered) to detect ALK rearrangements, and compared these with IHC and FISH. A total of 1128 NSCLC specimens were screened using conventional analyses, and a subset of 37 (15 ALK-positive, and 22 ALK-negative) samples were selected for NGS assays. Although AmpliSeq correctly detected 25/37 (67.6%) samples, 1/37 (2.7%) and 11/37 (29.7%) specimens were discordant and uncertain, respectively, requiring further validation. In contrast, Archer\textregisteredFusionPlex\textregisteredaccurately classified all samples and allowed the correct identification of one rare DCTN1-ALK fusion, one novel CLIP1-ALK fusion, and one novel GCC2-ALK transcript. Of particular interest, two out of three patients harboring these singular rearrangements were treated with and sensitive to crizotinib. These data show that Archer\textregisteredFusionPlex\textregisteredmay provide an effective and accurate alternative to FISH testing for the detection of known and novel ALK rearrangements in clinical diagnostic settings.

Domaines: Sciences du Vivant [q-bio]

Julie A. Vendrell, Sylvie Taviaux, Beno\ⁱt Béganton, Sylvain Godreuil, Patricia Audran, et al.. Detection of known and novel ALK fusion transcripts in lung cancer patients using next-generation sequencing approaches. Scientific Reports, 2017, 7 (1), pp.12510. ⟨10.1038/s41598-017-12679-8⟩. ⟨hal-01743905⟩