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

IF 1.6 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

{"title":"Mutations in Anaplastic Thyroid Carcinoma: An Analysis of the Japanese National Genomic Database","authors":"Hiromi Nagano, Hayato Matsumoto, Yumi Ando, Masatoyo Nakajo, Masaru Yamashita","doi":"10.1002/lio2.70110","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objectives</h3>\n \n <p>The purpose of this study is to investigate the genetic mutational status of anaplastic thyroid carcinoma (ATC) and its prognostic implications.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>The top 30 mutations in ATC were <i>TERT</i> (98/129), <i>TP53</i> (88/129), <i>BRAF</i> (72/129), <i>CDKN2A</i> (39/129), <i>CDKN2B</i> (29/129), <i>LTK</i> (26/129), <i>NRAS</i> (25/129), <i>KMT2D</i> (24/129), <i>PIK3CA</i> (26/129), <i>NOTCH3</i> (27/129), <i>NF2</i> (19/129), <i>MTAP</i> (17/129), <i>TET2</i> (16/129), <i>STK11</i> (15/129), <i>ATM</i> (14/129), <i>FANCA</i> (14/129), <i>NF1</i> (13/129), <i>DNMT3A</i> (13/129), <i>KIT</i> (13/129), <i>NOTCH1</i> (13/129), <i>EP300</i> (12/129), <i>BRCA2</i> (11/129), <i>CARD11</i> (11/129), <i>KEL</i> (11/129), <i>MSH3</i> (11/129), <i>PTEN</i> (11/129), <i>RICTOR</i> (11/129), <i>TSC1</i> (11/129), <i>ROS1</i> (10/129), and <i>KMT2A</i> (10/129) with 13.7 ± 0.5 (mean ± SEM) mutations/individual. Mutations in <i>BRAF</i> (<i>p</i> = 0.003), <i>PIK3CA</i> (<i>p</i> = 0.014), and <i>BRCA2</i> (<i>p</i> = 0.036) were associated with a significantly better prognosis, whereas mutations in <i>STK11</i> (<i>p</i> = 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, <i>p</i> = 3.5 × 10<sup>−3</sup>) for <i>PIK3CA</i>, 2.410 (1.054–5.515, <i>p</i> = 0.037) for <i>STK11</i>, and 0.157 (0.0376–0.659, <i>p</i> = 0.011) for <i>BRCA2</i>.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>In ATC, <i>PIK3CA</i>, and <i>BRCA2</i> mutations were associated with a better prognosis, and <i>STK11</i> mutation was associated with a poorer prognosis in this study.</p>\n </section>\n \n <section>\n \n <h3> Level of Evidence</h3>\n \n <p>3.</p>\n </section>\n </div>","PeriodicalId":48529,"journal":{"name":"Laryngoscope Investigative Otolaryngology","volume":"10 2","pages":""},"PeriodicalIF":1.6000,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lio2.70110","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Laryngoscope Investigative Otolaryngology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/lio2.70110","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"OTORHINOLARYNGOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

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.