Characterization of a novel complex BRAF mutation in a follicular variant papillary thyroid carcinoma
| Autor: | Isabella Merante Boschin, Eric Casal Ide, Luisa Barzon, Giulia Masi, Monia Pacenti, Maria Rosa Pelizzo, Enrico Lavezzo, Antonio Toniato, Stefano Toppo, Giorgio Palù |
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| Rok vydání: | 2008 |
| Předmět: |
Proto-Oncogene Proteins B-raf
medicine.medical_specialty endocrine system diseases kinase function prediction Endocrinology Diabetes and Metabolism Carcinoma Papillary Follicular Biology medicine.disease_cause Protein Structure Secondary Autoimmune thyroiditis Thyroid carcinoma Endocrinology Internal medicine medicine Humans cancer Amino Acid Sequence Thyroid Neoplasms Kinase activity Thyroid cancer b-raf activation Mutation Oncogene Cancer Exons General Medicine Middle Aged medicine.disease Cancer research Female V600E |
| Zdroj: | European Journal of Endocrinology. 159:77-80 |
| ISSN: | 1479-683X 0804-4643 |
| DOI: | 10.1530/eje-08-0239 |
| Popis: | IntroductionActivating mutations of the BRAF oncogene are frequently detected in papillary thyroid carcinoma (PTC) and have been associated with a worse prognosis. The amino acid substitution V600E accounts for 90% of all oncogenic BRAF mutations and is typically detected in classic PTCs, whereas other less frequent BRAF mutations seem to be associated with other PTC histotypes.CaseScreening for activating BRAF mutations in a series of 83 PTCs identified the most common V600E mutation in 39 cases (histologically, 38 classic PTCs and 1 sclerosing variant PTC) and a complex in-frame mutation involving amino acids V600–S605 in a stage III multicentric follicular variant PTC, occurring in a 50-year-old female patient, who was affected by hypothyroidism in autoimmune thyroiditis and had a family history of PTC and autoimmune thyroiditis. Since the identified BRAF mutation was novel in the literature, bioinformatic modeling was performed to predict its impact on BRAF activity. Although the mutation resulted in loss of a phosphorylation site in the activation loop of BRAF, it was predicted to increase BRAF kinase activity by mimicking an activating phosphorylation.ConclusionsThis study, which reports a new BRAF mutation, highlights the usefulness of bioinformatic modeling in the prediction of functional effects of new mutations and indicates that mutation-specific screening tests might miss some rare BRAF mutations. These facts should be taken into consideration in the molecular diagnosis of thyroid cancer and in the design of therapeutic protocols based on inhibitors of the BRAF pathway. |
| Databáze: | OpenAIRE |
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