Departments of Otolaryngology, Head and Neck Surgery, The University of Tokyo, Tokyo, Japan.
Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Clin Endocrinol (Oxf). 2024 Aug;101(2):170-179. doi: 10.1111/cen.15098. Epub 2024 Jun 9.
Anaplastic thyroid carcinoma (ATC) is considered a very aggressive carcinoma and has been difficult to treat with therapeutic strategies. This study examines the landscape of genomic alteration in ATC, including the BRAF V600E mutation, and its clinical implications.
DESIGN, PATIENTS AND MESUREMENT: A retrospective observational study was conducted using collected at the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) in Japan, utilizing comprehensive genomic profiling data from 102 ATC cases. Additionally, AACR-GENIE data from 267 cases were analysed for validation. Statistical methods, including the conditional Kendall tau statistic and χ tests, were employed for survival analysis and gene mutation comparisons.
Among 102 ATCs, BRAF, RAS, and other driver mutations were found in 83 cases (81.2%). The prevalence of BRAF V600E mutations was as high as 60%. Co-mutation analysis identified different genomic profiles in the BRAF, RAS, and wild-type groups. Despite the diverse molecular backgrounds, no significant differences in clinical variables and overall survival were observed. The analysis considering left-side amputation suggested that RAS mutations had a poorer prognosis. In the BRAF/RAS wild-type group, FGFR1 and NF1 were identified as driver mutations, with an accumulation of copy number variations and less TERT promoter mutations. This molecular subgrouping was also supported by the AACR-GENIE data.
Comprehensive genomic analysis of ATC in Japan revealed distinct molecular subgroups, highlighting the importance of BRAF V600E mutations, particularly V600E, as potential therapeutic targets and suggest the relevance of tailor-made therapeutic strategies based on genomic profiling.
间变性甲状腺癌（ATC）被认为是一种非常侵袭性的癌，其治疗策略一直难以实施。本研究探讨了 ATC 中的基因组改变图谱，包括 BRAF V600E 突变及其临床意义。
设计、患者和测量：本研究采用回顾性观察研究，在日本癌症基因组学和先进治疗中心（C-CAT）收集数据，利用来自 102 例 ATC 病例的综合基因组分析数据。此外，还对 267 例 AACR-GENIE 病例的数据进行了分析验证。统计方法包括条件 Kendall tau 统计和 χ 检验，用于生存分析和基因突变比较。
在 102 例 ATC 中，83 例（81.2%）存在 BRAF、RAS 和其他驱动基因突变。BRAF V600E 突变的发生率高达 60%。共突变分析在 BRAF、RAS 和野生型组中发现了不同的基因组图谱。尽管分子背景多样，但临床变量和总体生存率无显著差异。考虑左侧截肢的分析表明，RAS 突变的预后较差。在 BRAF/RAS 野生型组中，FGFR1 和 NF1 被鉴定为驱动突变，存在拷贝数变异的积累和较少的 TERT 启动子突变。这一分组也得到了 AACR-GENIE 数据的支持。
日本 ATC 的综合基因组分析揭示了不同的分子亚群，强调了 BRAF V600E 突变的重要性，特别是 V600E，作为潜在的治疗靶点，并提示基于基因组图谱制定个体化治疗策略的相关性。
