CD74-ROS1 fusion transcripts in resected non-small cell lung carcinoma

Abstract

The recent discovery of fusion oncokinases in a subset of non-small cell lung carcinomas (NSCLCs) is of considerable clinical interest, since NSCLCs that express such fusion oncokinases are reportedly sensitive to kinase inhibitors. To better understand the role of recently identified ROS1 and RET fusion oncokinases in pulmonary carcinogenesis, we examined 114 NSCLCs for SLC34A2-ROS1, EZR-ROS1, CD74-ROS1 and KIF5B-RET fusion transcripts using RT-polymerase chain reaction and subsequent sequencing analyses. Although the expression of SLC34A2-ROS1, EZR-ROS1, or KIF5B-RET fusion transcripts was not detected in any of the cases, the expression of CD74-ROS1 fusion transcripts was detected in one (0.9%) of the 114 NSCLCs. The fusion occurred between exon 6 of CD74 and exon 34 of ROS1 and was an in-frame alteration. The mutation was detected in a woman without a history of smoking. Histologically, the carcinoma was an adenocarcinoma with a predominant acinar pattern; notably, a mucinous cribriform pattern and a solid signet-ring cell pattern were also observed in part of the adenocarcinoma. ROS1 protein overexpression was immunohistochemically detected in a cancer-specific manner in both the primary cancer and the lymph node metastatic cancer. No somatic mutations were detected in the mutation cluster regions of the KRAS, EGFR, BRAF and PIK3CA genes and the entire coding region of p53 in the carcinoma, and the expression of ALK fusion was negative. The above results suggest that CD74-ROS1 fusion is involved in the carcinogenesis of a subset of NSCLCs and may contribute to the elucidation of the characteristics of ROS1 fusion-positive NSCLC in the future.