Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan.
Oncol Rep. 2013 Oct;30(4):1675-80. doi: 10.3892/or.2013.2630. Epub 2013 Jul 19.
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.
最近在一部分非小细胞肺癌（NSCLC）中发现融合致癌激酶，这在临床上具有重要意义，因为据报道，表达这种融合致癌激酶的 NSCLC 对激酶抑制剂敏感。为了更好地了解最近发现的 ROS1 和 RET 融合致癌激酶在肺肿瘤发生中的作用，我们使用 RT-聚合酶链反应和随后的测序分析，对 114 例 NSCLC 进行了 SLC34A2-ROS1、EZR-ROS1、CD74-ROS1 和 KIF5B-RET 融合转录本的检测。虽然在任何情况下均未检测到 SLC34A2-ROS1、EZR-ROS1 或 KIF5B-RET 融合转录本的表达，但在 114 例 NSCLC 中的 1 例（0.9%）中检测到 CD74-ROS1 融合转录本的表达。融合发生在 CD74 的外显子 6 和 ROS1 的外显子 34 之间，是一种框内改变。该突变发生在一位无吸烟史的女性中。组织学上，该癌为腺癌，以腺泡样为主；值得注意的是，部分腺癌中还观察到黏液性筛状和实性印戒细胞样模式。ROS1 蛋白在原发性和淋巴结转移性癌症中以癌特异性方式过表达。在癌中，KRAS、EGFR、BRAF 和 PIK3CA 基因的突变簇区以及 p53 的整个编码区中均未检测到体细胞突变，ALK 融合的表达为阴性。上述结果表明，CD74-ROS1 融合参与了一部分 NSCLC 的肿瘤发生，并且可能有助于阐明 ROS1 融合阳性 NSCLC 的特征。
