Molecular profile of Hürthle cell carcinomas: recurrent mutations in the Wnt/ß-catenin pathway.
Eur J Endocrinol
; 183(6): 647-656, 2020 Dec.
Article
en En
| MEDLINE
| ID: mdl-33120354
ABSTRACT
OBJECTIVE:
Genomic alterations in Hürthle cell carcinomas (HCC) include chromosomal losses, mitochondrial DNA mutations, and changes in the expression profile of the PI3K-AKT-mTOR and Wnt/ß-catenin pathways. This study aimed at characterizing the mutational profile of HCC.METHODS:
Next-generation sequencing (NGS) of 40 HCC using a 102-gene panel including, among others, the MAPK, PI3K-AKT-mTOR, Wnt/ß-catenin, and Notch pathways. HCC was widely invasive in 57.5%, and lymph node and distant metastases were diagnosed in 5% and 7.5% of cases. During follow-up, 10% of patients presented with persistent/recurrent disease, but there were no cancer-related deaths.RESULTS:
Genetic alterations were identified in 47.5% of HCC and comprised 190 single-nucleotide variants and 5 insertions/deletions. The Wnt/ß-catenin pathway was most frequently affected (30%), followed by MAPK (27.5%) and PI3K-AKT-mTOR (25%). FAT1 and APC were the most frequently mutated genes and present in 17.5%. RAS mutations were present in 12.5% but no BRAF mutation was found. There was no association between the mutational profile and clinicopathological features.CONCLUSIONS:
This series of HCC presents a wide range of mutations in the Wnt/ß-catenin, MAPK and PI3K-AKT-mTOR pathways. The recurrent involvement of Wnt/ß-catenin pathway, particularly mutations in APC and FAT1, are of particular interest. The data suggest that mutated FAT1 may represent a potential novel driver in HCC tumorigenesis and that the Wnt/ß-catenin pathway plays a critical role in this distinct thyroid malignancy.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Neoplasias de la Tiroides
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Cadherinas
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Adenoma Oxifílico
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Proteína de la Poliposis Adenomatosa del Colon
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Beta Catenina
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Vía de Señalización Wnt
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Eur J Endocrinol
Asunto de la revista:
ENDOCRINOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Brasil