دورية أكاديمية
Molecular profile of Hürthle cell carcinomas: recurrent mutations in the Wnt/β-catenin pathway.
| العنوان: | Molecular profile of Hürthle cell carcinomas: recurrent mutations in the Wnt/β-catenin pathway. |
|---|---|
| المؤلفون: | Santana NO; Laboratorio de Endocrinologia Celular e Molecular (LIM25), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil., Lerario AM; Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA., Schmerling CK; Pathology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil., Marui S; Laboratorio de Endocrinologia Celular e Molecular (LIM25), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil., Alves VAF; Pathology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil., Hoff AO; Endocrinology, Instituto do Cancer do Estado de Sao Paulo, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil., Kopp P; Division of Endocrinology, Diabetes and Metabolism, University of Lausanne, Lausanne, Switzerland.; Division of Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA., Danilovic DLS; Laboratorio de Endocrinologia Celular e Molecular (LIM25), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.; Endocrinology, Instituto do Cancer do Estado de Sao Paulo, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil. |
| المصدر: | European journal of endocrinology [Eur J Endocrinol] 2020 Dec; Vol. 183 (6), pp. 647-656. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 9423848 Publication Model: Print Cited Medium: Internet ISSN: 1479-683X (Electronic) Linking ISSN: 08044643 NLM ISO Abbreviation: Eur J Endocrinol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2023- : Oxford : Oxford University Press Original Publication: Oslo, Norway : Scandinavian University Press, c1994- |
| مواضيع طبية MeSH: | Adenoma, Oxyphilic/*genetics , Adenomatous Polyposis Coli Protein/*genetics , Cadherins/*genetics , Thyroid Neoplasms/*genetics , Wnt Signaling Pathway/*genetics , beta Catenin/*genetics, Aged ; Female ; Gene Expression Regulation, Neoplastic/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Retrospective Studies |
| مستخلص: | 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/β-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/β-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/β-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/β-catenin, MAPK and PI3K-AKT-mTOR pathways. The recurrent involvement of Wnt/β-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/β-catenin pathway plays a critical role in this distinct thyroid malignancy. |
| المشرفين على المادة: | 0 (APC protein, human) 0 (Adenomatous Polyposis Coli Protein) 0 (CTNNB1 protein, human) 0 (Cadherins) 0 (FAT1 protein, human) 0 (beta Catenin) |
| SCR Disease Name: | Thyroid cancer, Hurthle cell |
| تواريخ الأحداث: | Date Created: 20201029 Date Completed: 20201110 Latest Revision: 20220417 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1530/EJE-20-0597 |
| PMID: | 33120354 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1479-683X |
|---|---|
| DOI: | 10.1530/EJE-20-0597 |