Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2024 Aug;101(2):170-179.
doi: 10.1111/cen.15098. Epub 2024 Jun 9.

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

Yuki Saito  1 , Hidenori Kage  2 , Kenya Kobayashi  1 , Teru Kamogashira  1 , Osamu Fukuoka  1 , Koji Yamamura  1 , Satoshi Yamashita  3 , Masahiko Tanabe  3 , Katsutoshi Oda  4 , Kenji Kondo  1
Affiliations
Observational Study

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

Yuki Saito et al. Clin Endocrinol (Oxf). 2024 Aug.

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.

Keywords: BRAF; C‐CAT; RAS; comprehensive genomic profiing; thyroid anaplastic carcinoma.

PubMed Disclaimer

References

REFERENCES

    1. Giuffrida D, Gharib H. Anaplastic thyroid carcinoma: current diagnosis and treatment. Ann Oncol. 2000;11:1083‐1090.
    1. Brose MS, Nutting CM, Jarzab B, et al. Sorafenib in radioactive iodine‐refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double‐blind, phase 3 trial. The Lancet. 2014;384:319‐328.
    1. Schlumberger M, Tahara M, Wirth LJ, et al. Lenvatinib versus placebo in radioiodine‐refractory thyroid cancer. N Engl J Med. 2015;372:621‐630.
    1. Higashiyama T, Sugino K, Hara H, et al. Phase II study of the efficacy and safety of lenvatinib for anaplastic thyroid cancer (HOPE). Eur J Cancer. 2022;173:210‐218.
    1. Hanauer D, Rhodes D, Sinha‐Kumar C, Chinnaiyan A. Bioinformatics approaches in the study of cancer. Curr Mol Med. 2007;7:133‐141.

Publication types