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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Molecular profile of Hurthle cell carcinomas: recurrent mutations in the Wnt/beta-caten n pathway

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Santana, Nathalie Oliveira [1] ; Lerario, Antonio Marcondes [2] ; Schmerling, Claudia Kliemann [3] ; Marui, Suemi [1] ; Ferreira Alves, Venancio Avancini [3] ; Hoff, Ana O. [4] ; Kopp, Peter [5, 6] ; Seguro Danilovic, Debora Lucia [1, 4]
Total Authors: 8
[1] Univ Sao Paulo, Hosp Clin HCFMUSP, Fac Med, Lab Endocrinol Celular & Mol LIM25, Sao Paulo - Brazil
[2] Univ Michigan, Dept Internal Med, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 - USA
[3] Univ Sao Paulo, Hosp Clin HCFMUSP, Fac Med, Pathol, Sao Paulo - Brazil
[4] Univ Sao Paulo, Fac Med, Inst Canc Estado Sao Paulo, Endocrinol, Sao Paulo - Brazil
[5] Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 - USA
[6] Univ Lausanne, Div Endocrinol Diabet & Metab, Lausanne - Switzerland
Total Affiliations: 6
Document type: Journal article
Source: EUROPEAN JOURNAL OF ENDOCRINOLOGY; v. 183, n. 6, p. 647-656, DEC 2020.
Web of Science Citations: 0

Objective: Genomic alterations in Hurthle cell carcinomas (HCC) include chromosomal losses, mitochondria! DNA mutations, and changes in the expression profile of the PI3K-AKT-mTOR and Wnt/beta-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/beta-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/beta-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/beta-catenin, MAPK and PI3K-AKT-mTOR pathways. The recurrent involvement of Wnt/beta-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/p-catenin pathway plays a critical role in this distinct thyroid malignancy. (AU)

Grantee:Debora Lucia Seguro Danilovic
Support Opportunities: Regular Research Grants