Saeed-Vafa Daryoush, Chatzopoulos Kyriakos, Hernandez-Prera Juan, Cano Pedro, Saller James J, Hallanger Johnson Julie E, McIver Bryan, Boyle Theresa A
H. Lee Moffitt Cancer Center, Tampa, FL, United States.
Front Genet. 2024 Mar 19;15:1377158. doi: 10.3389/fgene.2024.1377158. eCollection 2024.
Medullary thyroid carcinoma (MTC) is an aggressive cancer that is often caused by driver mutations in . Splice site variants (SSV) reflect changes in mRNA processing, which may alter protein function. SSVs have been described in thyroid tumors in general but have not been extensively studied in MTC. The prevalence of SSVs was evaluated in 3,624 cases with next generation sequence reports, including 25 MTCs. Fisher exact analysis was performed to compare SSV frequency in cancers with/without a diagnosis of MTC. All 25 MTCs had at least one of the two most common SSVs versus 0.3% of 3,599 cancers with other diagnoses ( < 0.00001). The 11 cancers with non-MTC diagnoses that had the common SSVs were 4 neuroendocrine cancers, 4 non-small cell lung carcinomas, 2 non-MTC thyroid cancers, and 1 melanoma. All 25 MTCs analyzed had at least one of the two most common SSVs, including 4 with no identified mutational driver. The identification of SSVs in all MTCs, but rarely in other cancer types, demonstrates that these SSVs distinguish MTCs from other cancer types. Future studies are needed to investigate whether these SSVs play a pathogenic role in MTC.
甲状腺髓样癌（MTC）是一种侵袭性癌症，通常由[具体基因]中的驱动突变引起。剪接位点变异（SSV）反映了mRNA加工过程中的变化，这可能会改变蛋白质功能。一般来说，SSV已在甲状腺肿瘤中有所描述，但在MTC中尚未得到广泛研究。在3624例有下一代测序报告的病例中评估了SSV的患病率，其中包括25例MTC。进行Fisher精确分析以比较有/无MTC诊断的癌症中SSV的频率。所有25例MTC均至少有两种最常见SSV中的一种，而在3599例其他诊断的癌症中这一比例为0.3%（P<0.00001）。11例有非MTC诊断且有常见SSV的癌症分别为4例神经内分泌癌、4例非小细胞肺癌、2例非MTC甲状腺癌和1例黑色素瘤。分析的所有25例MTC均至少有两种最常见SSV中的一种，其中4例未发现突变驱动因素。在所有MTC中均发现了SSV，但在其他癌症类型中很少见，这表明这些SSV可将MTC与其他癌症类型区分开来。未来需要进行研究以调查这些SSV在MTC中是否发挥致病作用。
