Identification of a novel RSRC1-ALK (R6: A20) fusion using next-generation sequencing technique

Abstract

Non-small-cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase (ALK) fusion showed promising responses to ALK tyrosine kinase inhibitors (TKIs). In this study, fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), next generation sequencing (NGS) and Sanger sequencing were performed to identify the presence of ALK fusion, to investigate whether the patient may benefit from TKI therapy. Postoperative pathological analysis indicated invasive adenocarcinoma with mainly mucinous type and partial micropapillary type in left lower lung. Minimally invasive adenocarcinoma was seen in left upper lung, with mainly acinar type. NGS detected a novel RSRC1-ALK (R6: A20) fusion in left lower lobe sample, which was presented as the fusion of exon 6 of RSRC1 and exon 20 of ALK gene. Sanger sequencing validated the fusion. Break rearrangement signal of ALK gene was detected in 80% of tumor cells. Immunohistochemistry showed ALK positive expression in lung. For the treatment, the patient received ensartinib hydrochloride with a dose of 225 mg per day. He was in a state of progression-free survival for at least 24 months in follow-up with no complications. NGS can be used for exploring treatment options for NSCLC patients with ALK fusion.