Characterization of Driver Mutations in Anaplastic Thyroid Carcinoma Identifies RAS and PIK3CA Mutations as Negative Survival Predictors

Cancers
Wei-An LaiJen-Fan Hang

Abstract

Anaplastic thyroid carcinoma (ATC) is rare but highly aggressive. We investigated the association of selected driver mutations, including BRAF, RAS,PIK3CA, TERT promoter, TP53, POLE, and mismatch repair deficiency (MMR-D) with the clinicopathological features of ATC to identify prognostic and predictive biomarkers. Thirty-nine retrospective cases from pathology archives were enrolled for clinicopathology analysis and immunohistochemistry, and 27 cases had sufficient specimens for further molecular testing using targeted next-generation sequencing and mass spectrometry. BRAFV600E and RAS mutations were identified in 25.9% and 40.7% of ATC, respectively. BRAFV600E mutation was significantly associated with coexisting papillary thyroid carcinoma (p = 0.009) and RAS mutations with female gender (p = 0.012). In univariant analysis, the non-BRAF/RAS tumors were significantly associated with the presence of a sarcomatoid pattern (p = 0.045). PIK3CA, TERT promoter, and TP53 mutations were identified in 14.8%, 81.5%, and 70.4% of cases, respectively. No MMR-D or POLE mutations were detected. In survival analyses, RAS and PIK3CA mutations were significantly associated with inferior outcomes (p = 0.03 and p = 0.006, respectively). In conc...Continue Reading

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Citations

Dec 19, 2020·International Journal of Molecular Sciences·Eun-Kyung KimYoo Seung Chung
Jun 6, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Theodora PappaIñigo Landa

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Methods Mentioned

BETA
surgical resection
biopsy
PCR
Assay

Software Mentioned

MEM
R
TYPER
BWA
R Foundation for Statistical Computing
Assay Designer
MassARRAY Analyzer

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