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Sci Rep. 2017 Oct 2;7(1):12510. doi: 10.1038/s41598-017-12679-8.

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

Author information

1
CHU Montpellier, Arnaud de Villeneuve Hospital, Department of Pathology, Montpellier, Université de Montpellier, Montpellier, France.
2
Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, Université de Montpellier, Institut du Cancer de Montpellier (ICM), Montpellier, France.
3
CHU Montpellier, Arnaud de Villeneuve Hospital, Department of Bacteriology, Université de Montpellier, Montpellier, France.
4
Institut du Cancer de Montpellier (ICM), Department of Biopathology, Montpellier, France.
5
Department of Pathology, Institut Universitaire du Cancer Toulouse Oncopole, CHU de Toulouse, Toulouse, France.
6
Thoracic Oncology Department, Larrey Hospital, University Hospital of Toulouse, Toulouse, France.
7
CHU Montpellier, Arnaud de Villeneuve Hospital, Department of Thoracic Oncology, Université de Montpellier, Montpellier, France.
8
Laboratoire d'excellence Labex TOUCAN, Toulouse, France.
9
CHU Montpellier, Arnaud de Villeneuve Hospital, Department of Pathology, Montpellier, Université de Montpellier, Montpellier, France. j-solassol@chu-montpellier.fr.
10
Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, Université de Montpellier, Institut du Cancer de Montpellier (ICM), Montpellier, France. j-solassol@chu-montpellier.fr.

Abstract

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®FusionPlex®) 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®FusionPlex® accurately 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®FusionPlex® may provide an effective and accurate alternative to FISH testing for the detection of known and novel ALK rearrangements in clinical diagnostic settings.

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