Abstract：
OBJECTIVE: 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.
UNASSIGNED: 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 χ2 tests, were employed for survival analysis and gene mutation comparisons.
RESULTS: 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.
CONCLUSIONS: 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.
UNASSIGNED: 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 χ2 tests, were employed for survival analysis and gene mutation comparisons.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
目的：间变性甲状腺癌（ATC）被认为是一种侵袭性非常强的癌，难以用治疗策略治疗。这项研究考察了ATC基因组改变的景观，包括BRAFV600E突变,及其临床意义。
■使用日本癌症基因组学和高级治疗中心（C-CAT）进行了一项回顾性观察研究，利用102例ATC病例的综合基因组分析数据。此外,对267例病例的AACR-GENIE数据进行了验证分析。统计方法，包括条件Kendalltau统计量和χ2检验，用于生存分析和基因突变比较。
结果：在102个ATC中，BRAF,RAS,83例(81.2%)发现其他驱动突变。BRAFV600E突变的患病率高达60%。共突变分析确定了BRAF中不同的基因组谱，RAS,和野生型组。尽管分子背景不同,在临床变量和总生存期方面没有观察到显著差异.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，具有拷贝数变异的积累和较少的TERT启动子突变。AACR-GENIE数据也支持该分子亚组。
结论：日本ATC的综合基因组分析揭示了不同的分子亚群，强调BRAFV600E突变的重要性，特别是V600E，作为潜在的治疗靶点，并建议基于基因组谱的量身定制的治疗策略的相关性。
■使用日本癌症基因组学和高级治疗中心（C-CAT）进行了一项回顾性观察研究，利用102例ATC病例的综合基因组分析数据。此外,对267例病例的AACR-GENIE数据进行了验证分析。统计方法，包括条件Kendalltau统计量和χ2检验，用于生存分析和基因突变比较。
结果：在102个ATC中，BRAF,RAS,83例(81.2%)发现其他驱动突变。BRAFV600E突变的患病率高达60%。共突变分析确定了BRAF中不同的基因组谱，RAS,和野生型组。尽管分子背景不同,在临床变量和总生存期方面没有观察到显著差异.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，具有拷贝数变异的积累和较少的TERT启动子突变。AACR-GENIE数据也支持该分子亚组。
结论：日本ATC的综合基因组分析揭示了不同的分子亚群，强调BRAFV600E突变的重要性，特别是V600E，作为潜在的治疗靶点，并建议基于基因组谱的量身定制的治疗策略的相关性。
