Intergenic Breakpoints Identified by DNA Sequencing Confound Targetable Kinase Fusion Detection in NSCLC

Introduction: Next-generation sequencing (NGS) based on genomic DNA has been widely applied for gene rearrangement detection in patients with NSCLC. However, intergenic-breakpoint fusions, in which one or both genomic breakpoints localize to intergenic regions, confound kinase fusion detection. We evaluated the function of intergenic-breakpoint fusions with multiplex molecular testing approaches... Conclusions: Intergenic-breakpoint fusions detected by DNA sequencing confound kinase fusion detection in NSCLC, as functional fusion transcripts may be generated or not. Additional validation testing using RNA/protein assay should be performed in intergenic-breakpoint fusion cases to guide optimal treatment. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2020.02.023

Authors: Weihua Li, Yutao Liu, Wenbin Li, Li Chen, Jianming Ying

Case StudyKirk SmithJuly 1, 2020Intergenic breakpoint, Kinase fusion, Next-generation sequencing, Non–small cell lung cancer, Targeted therapy

Fusion of ALK to the melanophilin gene MLPH in pediatric Spitz nevi

Spitzoid neoplasms typically affect young individuals and include Spitz nevus, atypical Spitz tumor, and Spitzoid melanoma. Spitz tumors can exhibit gene fusions involving the receptor tyrosine kinases NTRK1, NTRK3, ALK, ROS1, RET, or MET, or the serine-threonine kinase BRAF. Because most studies have been based on adult cases, we studied ALK fusions in Spitz nevi occurring in pediatric patients. Twenty-seven cases were screened for ALK expression by immunohistochemistry, and 6 positive cases were identified. These cases were studied further using the TruSight RNA Fusion Panel, and in 4 cases, exon 20 of the ALK gene was found to be fused to exon 14 of the MLPH (melanophilin) gene, a gene fusion that has only been reported in a Spitz nevus in an adult. The remaining 2 cases showed no fusion of ALK with any gene. The cases with the MLPH-ALK fusion showed a similar histology to that described for Spitz nevi with ALK fusions, with spindle-shaped and epithelioid melanocytes in fusiform nes..... READ ARTICLE

Human Pathology DOI:10.1016/j.humpath.2019.03.002

Authors: Catherine T. Chung, Paula Marrano, David Swanson, Brendan C. Dickson, Paul Scott Thorner

Case StudyKirk SmithMay 1, 2019Spitz nevus, ALK, MLPH, Melanophilin, Kinase fusion, FISH, TruSight RNA Fusion Panel, pediatric