间变性甲状腺癌的突变：日本国家基因组数据库的分析

IF 1.7 4区医学 Q2 OTORHINOLARYNGOLOGY

Laryngoscope Investigative Otolaryngology Pub Date : 2025-03-07 DOI:10.1002/lio2.70110

Hiromi Nagano, Hayato Matsumoto, Yumi Ando, Masatoyo Nakajo, Masaru Yamashita

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引用次数: 0

摘要

目的探讨间变性甲状腺癌（ATC）的基因突变状况及其预后意义。方法分析2019年6月至2024年6月在日本国立癌症中心癌症基因组学和高级治疗中心（C-CAT）注册的129例连续ATC患者的数据。通过FoundationOne CDx或Liquid CDx下一代测序检测遗传改变。通过log-rank检验和Cox比例风险模型确定患者的生存期。结果ATC前30位突变分别为TERT（98/129）、TP53（88/129）、BRAF（72/129）、CDKN2A（39/129）、CDKN2B（29/129）、LTK（26/129）、NRAS（25/129）、KMT2D（24/129）、PIK3CA（26/129）、NOTCH3（27/129）、NF2（19/129）、MTAP（17/129）、TET2（16/129）、STK11（15/129）、ATM（14/129）、FANCA（14/129）、NF1（13/129）、DNMT3A（13/129）、KIT（13/129）、NOTCH1（13/129）、EP300（12/129）、BRCA2（11/129）、CARD11（11/129）、KEL（11/129）、MSH3（11/129）、PTEN（11/129）、RICTOR（11/129）、TSC1（11/129）、ROS1（10/129）和KMT2A（10/129）突变为13.7±0.5（平均±SEM）个/个体。经log-rank检验，BRAF （p = 0.003）、PIK3CA （p = 0.014）和BRCA2 （p = 0.036）突变与明显较好的预后相关，而STK11突变（p = 0.024）与明显较差的预后相关。PIK3CA、STK11和BRCA2突变的风险比分别为0.248 （95% CI, 0.0973-0.633, p = 3.5 × 10−3）、2.410 （1.054-5.515,p = 0.037）和0.157 （0.0376-0.659,p = 0.011）。在本研究中，ATC中PIK3CA和BRCA2突变与预后较好相关，STK11突变与预后较差相关。证据水平

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Mutations in Anaplastic Thyroid Carcinoma: An Analysis of the Japanese National Genomic Database

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Mutations in Anaplastic Thyroid Carcinoma: An Analysis of the Japanese National Genomic Database

Objectives

The purpose of this study is to investigate the genetic mutational status of anaplastic thyroid carcinoma (ATC) and its prognostic implications.

Methods

Data were analyzed for 129 consecutive patients with ATC registered at the Japan National Cancer Center, Center for Cancer Genomics and Advanced Therapeutics (C-CAT) between June 2019 and June 2024. Genetic alterations were determined by FoundationOne CDx or Liquid CDx next-generation sequencing. The survival of patients was determined by the log-rank test and a Cox proportional hazards model.

Results

The top 30 mutations in ATC were TERT (98/129), TP53 (88/129), BRAF (72/129), CDKN2A (39/129), CDKN2B (29/129), LTK (26/129), NRAS (25/129), KMT2D (24/129), PIK3CA (26/129), NOTCH3 (27/129), NF2 (19/129), MTAP (17/129), TET2 (16/129), STK11 (15/129), ATM (14/129), FANCA (14/129), NF1 (13/129), DNMT3A (13/129), KIT (13/129), NOTCH1 (13/129), EP300 (12/129), BRCA2 (11/129), CARD11 (11/129), KEL (11/129), MSH3 (11/129), PTEN (11/129), RICTOR (11/129), TSC1 (11/129), ROS1 (10/129), and KMT2A (10/129) with 13.7 ± 0.5 (mean ± SEM) mutations/individual. Mutations in BRAF (p = 0.003), PIK3CA (p = 0.014), and BRCA2 (p = 0.036) were associated with a significantly better prognosis, whereas mutations in STK11 (p = 0.024) was associated with a significantly worse prognosis, as determined by log-rank tests. The hazard ratios for cases with these mutations were 0.248 (95% CI, 0.0973–0.633, p = 3.5 × 10⁻³) for PIK3CA, 2.410 (1.054–5.515, p = 0.037) for STK11, and 0.157 (0.0376–0.659, p = 0.011) for BRCA2.

Conclusions

In ATC, PIK3CA, and BRCA2 mutations were associated with a better prognosis, and STK11 mutation was associated with a poorer prognosis in this study.