Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Thyroid. 2024 Oct;34(10):1308-1313. doi: 10.1089/thy.2024.0224. Epub 2024 Aug 27.
Receptor tyrosine kinase (RTK) fusions of , and are enriched among pediatric thyroid cancer patients with metastatic and persistent disease, and their oncoproteins represent attractive drug targets. We performed RNA-sequencing in a papillary thyroid cancer (PTC) lacking other frequent driver alterations. We report a novel RTK fusion, -insulin-like growth factor 1 receptor gene (), in a 17-year-old female patient with angioinvasive follicular variant PTC. The in-frame fusion protein preserves the cholinesterase-like domain of TG with dimerization properties and the transmembrane and kinase domain of IGF1R. The tumor sample shows increased mRNA expression and tyrosine kinase phosphorylation, augmentation of Mitogen activated protein kinase (MAPK) transcriptional output genes, and decreased levels. We reveal a novel targetable kinase fusion oncogene in thyroid cancer which is not incorporated in different thyroid-specific sequencing panels. The integration of fusion screening in the next versions of thyroid-specific targeted next-generation sequencing panels may be beneficial to thyroid cancer patients.
受体酪氨酸激酶（RTK）融合的 、 和 在转移性和持续性疾病的儿科甲状腺癌患者中丰富存在，其癌蛋白代表了有吸引力的药物靶点。我们对一种缺乏其他常见驱动突变的甲状腺乳头状癌（PTC）进行了 RNA 测序。我们报道了一种新的 RTK 融合，-胰岛素样生长因子 1 受体基因（），在一名 17 岁女性具有侵袭性血管滤泡变体 PTC 患者中。该融合蛋白保留了 TG 的胆碱酯酶样结构域，具有二聚化特性以及 IGF1R 的跨膜和激酶结构域。肿瘤样本显示 mRNA 表达和酪氨酸激酶磷酸化增加，促分裂原激活的蛋白激酶（MAPK）转录输出基因增加，而 水平降低。我们在甲状腺癌中揭示了一种新的可靶向激酶融合致癌基因，它不包含在不同的甲状腺特异性测序面板中。在甲状腺特异性靶向下一代测序面板的新版本中整合 融合筛选可能对甲状腺癌患者有益。
