Fusion Oncogenes Are Associated With Increased Metastatic Capacity and Persistent Disease in Pediatric Thyroid Cancers.
Fusion Oncogenes Are Associated With Increased Metastatic Capacity and Persistent Disease in Pediatric Thyroid Cancers.
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DOI：
10.1200/jco.21.01861
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发表时间：
2022-04-01
期刊：
影响因子：
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通讯作者：
Bauer AJ
中科院分区：
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作者：
Franco AT;Ricarte-Filho JC;Isaza A;Jones Z;Jain N;Mostoufi-Moab S;Surrey L;Laetsch TW;Li MM;DeHart JC;Reichenberger E;Taylor D;Kazahaya K;Adzick NS;Bauer AJ
2014 年，癌症基因组图谱项目报告的对 496 个成人乳头状甲状腺癌样本进行综合多平台分析的数据表明，将甲状腺癌重新分类为分子亚型（RAS 样和 BRAF 样）比单独依赖病理学分类更好地反映临床行为。本研究的目的是对儿科分化型甲状腺癌 (DTC) 中常见的致癌变异进行分类，并研究突变亚型分类是否与儿科 DTC 的转移风险和初始治疗反应相关。对 131 名儿科患者的 DTC 完成了体细胞癌症基因组分析。 DTC 被分为 RAS 突变型 (H-K-NRAS)、BRAF 突变型 (BRAF p.V600E) 和 RET/NTRK 融合型（RET、NTRK1 和 NTRK3 融合型），以确定亚型分类之间在病理数据（美国癌症 TNM 联合委员会）以及初始治疗完成 1 年后的治疗反应方面的差异。基于突变的亚型类别在大多数变量中都很重要，包括诊断时的年龄、转移行为和 1 年缓解的可能性。与 RAS 或 BRAF-mut 亚组的患者相比，RET/NTRK 融合的患者出现晚期淋巴结和远处转移的可能性明显更高，并且在 1 年内获得缓解的可能性更小。我们的数据支持，儿科 DTC 的遗传亚型比单独依赖病理分类更准确地反映临床行为，其中 RET/NTRK 融合患者的预后比 BRAF 突变疾病患者更差。未来的试验应考虑将分子亚型纳入风险分层。
In 2014, data from a comprehensive multiplatform analysis of 496 adult papillary thyroid cancer samples reported by The Cancer Genome Atlas project suggested that reclassification of thyroid cancer into molecular subtypes, RAS-like and BRAF-like, better reflects clinical behavior than sole reliance on pathologic classification. The aim of this study was to categorize the common oncogenic variants in pediatric differentiated thyroid cancer (DTC) and investigate whether mutation subtype classification correlated with the risk of metastasis and response to initial therapy in pediatric DTC. Somatic cancer gene panel analysis was completed on DTC from 131 pediatric patients. DTC were categorized into RAS-mutant (H-K-NRAS), BRAF-mutant (BRAF p.V600E), and RET/NTRK fusion (RET, NTRK1, and NTRK3 fusions) to determine differences between subtype classification in regard to pathologic data (American Joint Committee on Cancer TNM) as well as response to therapy 1 year after initial treatment had been completed. Mutation-based subtype categories were significant in most variables, including age at diagnosis, metastatic behavior, and the likelihood of remission at 1 year. Patients with RET/NTRK fusions were significantly more likely to have advanced lymph node and distant metastasis and less likely to achieve remission at 1 year than patients within RAS- or BRAF-mut subgroups. Our data support that genetic subtyping of pediatric DTC more accurately reflects clinical behavior than sole reliance on pathologic classification with patients with RET/NTRK fusions having worse outcomes than those with BRAF-mutant disease. Future trials should consider inclusion of molecular subtype into risk stratification.