ETV6-NTRK3 and STRN-ALK kinase fusions are recurrent events in papillary thyroid cancer of adult population

Autor(es)

Bastos, Andre Uchimura ^[1] ; de Jesus, Ana Carolina ^[1] ; Cerutti, Janete Maria ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Morfol & Genet, Genet Bases Thyroid Tumors Lab, Disciplina Genet, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF ENDOCRINOLOGY; v. 178, n. 1, p. 83-91, JAN 2018.
• Citações Web of Science: 9

Resumo

Objective: PTC-specific analysis identified novel fusions involving RET, BRAF, NTRK1, NTRK3, AGK and ALK genes in adults and pediatric PTCs. Although many novel fusions are PTC-specific events and, therefore, are ideal for diagnosis purposes, validation across additional and larger patient cohorts is essential for introducing these potential diagnostic or prognostic biomarkers into the clinical practice. As most of the BRAF, NTRK3 and ALK fusions were initially found in pediatric PTC or in more aggressive thyroid carcinomas, and there is a great disparity across population, in this study, we screened a large set of adult-sporadic PTC cases for the most prevalent kinase fusion lately described in the TCGA. Design and methods: The prevalence of the fusions was determined by RT-PCR in 71 classical PTC, 45 follicular variants of PTC (FVPTC), 19 follicular thyroid adenomas (FTAs) and 22 follicular thyroid carcinomas (FTCs). Results: ETV6-NTRK3 was exclusively found in FVPTC, in both encapsulated and infiltrative variants, but was not found in FTAs and FTCs. STRN-ALK was found in both classical PTC and FVPTC. No AGK-BRAF fusion was identified in this series, endorsing that AGK-BRAF is a genetic event mainly associated with pediatric PTCs. Conclusions: The identification of kinase fusions in thyroid carcinomas helps to expand our knowledge about the landscape of oncogenic alterations in PTC. As ETV6-NTRK3 and STRN-ALK are recurrent and not identified in benign lesions, they can certainly help with diagnosis of thyroid nodules. Further analysis is needed to define if they can also be useful for prognosis and guiding therapy. (AU)

• Processo FAPESP: 12/06221-6 - Caracterização funcional da dupla mutação BRAFV600E + RET/PTC3 em carcinoma papilífero da tiroide
• Beneficiário: André Uchimura Bastos
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 13/03867-5 - Análise da variação no número de cópias (CNV) de segmentos de DNA em pacientes de uma família com síndrome nem 2ª e mutação p.G533C no gene RET: identificação de regiões associadas à gênese e progressão do carcinoma medular da tiróide
• Beneficiário: Janete Maria Cerutti
• Modalidade de apoio: Auxílio à Pesquisa - Regular