Abstract: Intergenic-gene fusion detected by DNA-seq is particularly confusing for drug selection since the function of the intergenic region located upstream is unknown. We reported a case of a 49-year-old male with advanced lung adenocarcinoma, who was detected FBXO11 (intergenic)-ALK (exon 20-29) by DNA-seq, and FISH analysis revealed a positive result. The patient was treated with crizotinib and achieved a PR. The canonical EML4 (exon 1-13)-ALK (exon 20-29) fusion verified by RNA-seq suggested a complex EML4 (exon 1-13)-FBXO11 (intergenic)-ALK (exon 20-29) tripartite rearrangement at the DNA level. Our case emphasized the necessity of RNA-seq for verifying intergenic-gene fusion. Simultaneously, the pathogenic germline SLX4 variant and extensive CNVs of DNA segment were detected by DNA-seq deserves our attention.
Keywords: intergenic fusion, lung adenocarcinoma, ALK, SLX4, chromothripsis