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Comprehensive genomic profiling from C-CAT database unveiled over 80% presence of oncogenic drivers in anaplastic thyroid carcinoma including BRAF, RAS family, NF1, and FGFR1.
Saito, Yuki; Kage, Hidenori; Kobayashi, Kenya; Kamogashira, Teru; Fukuoka, Osamu; Yamamura, Koji; Yamashita, Satoshi; Tanabe, Masahiko; Oda, Katsutoshi; Kondo, Kenji.
Afiliação
  • Saito Y; Departments of Otolaryngology, Head and Neck Surgery, The University of Tokyo, Tokyo, Japan.
  • Kage H; Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Kobayashi K; Departments of Otolaryngology, Head and Neck Surgery, The University of Tokyo, Tokyo, Japan.
  • Kamogashira T; Departments of Otolaryngology, Head and Neck Surgery, The University of Tokyo, Tokyo, Japan.
  • Fukuoka O; Departments of Otolaryngology, Head and Neck Surgery, The University of Tokyo, Tokyo, Japan.
  • Yamamura K; Departments of Otolaryngology, Head and Neck Surgery, The University of Tokyo, Tokyo, Japan.
  • Yamashita S; Department of Breast and Endocrine Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Tanabe M; Department of Breast and Endocrine Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Oda K; Division of Integrative Genomics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Kondo K; Departments of Otolaryngology, Head and Neck Surgery, The University of Tokyo, Tokyo, Japan.
Clin Endocrinol (Oxf) ; 101(2): 170-179, 2024 Aug.
Article em En | MEDLINE | ID: mdl-38853441
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. 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 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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Glândula Tireoide / Proteínas Proto-Oncogênicas B-raf / Receptor Tipo 1 de Fator de Crescimento de Fibroblastos / Carcinoma Anaplásico da Tireoide / Mutação Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged País como assunto: Asia Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Glândula Tireoide / Proteínas Proto-Oncogênicas B-raf / Receptor Tipo 1 de Fator de Crescimento de Fibroblastos / Carcinoma Anaplásico da Tireoide / Mutação Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged País como assunto: Asia Idioma: En Ano de publicação: 2024 Tipo de documento: Article