Fusion Oncogenes Are the Main Genetic Events Found in Sporadic Papillary Thyroid Carcinomas from Children

Author(s)

Vieira Cordioli, Maria Isabel C. ; Moraes, Lais ; Bastos, Andre U. ; Besson, Paloma ; de Seixas Alves, Maria Teresa ; Delcelo, Rosana ; Monte, Osmar ; Longui, Carlos ; Cury, Adriano Namo ; Cerutti, Janete M.

• Document type: Journal article
• Source: THYROID; v. 27, n. 2, p. 182-188, FEB 2017.
• Web of Science Citations: 14

Abstract

Background: Previous studies reported significant differences in the clinical presentation and outcomes of papillary thyroid carcinoma (PTC) in pediatric patients compared with adults. Previous studies have suggested that the clinicopathological differences observed between pediatric and adult PTCs may be due the existence of distinct genetic alterations. However, the knowledge of genetic events in pediatric PTCs is based primarily on studies in radiation-exposed PTCs or in the few studies that enrolled predominantly adolescent patients. The aim of this study was to characterize the known oncogenic alterations of the MAPK pathway found in adult and radiation-exposed PTCs in a cohort of predominantly sporadic pediatric PTC patients. Methods: Thirty-five pediatric PTCs were screened for the most prevalent fusions (RET/PTC1, RET/PTC2, RET/PTC3, ETV6-NTRK3, and AGK-BRAF) and point mutations (BRAF(V600E) and NRAS(Q61)) described in sporadic pediatric PTCs. The mutational status was correlated with clinicopathological data. Results: Mutations were found in 20 out of 35 (57%) PTC cases. Fusion oncogenes were the main genetic alterations found. RET/PTC1-3 rearrangements were found in 13 (37%), ETV6-NTRK3 in 3 (9%), AGK-BRAF in 4 (11%), and BRAF(V600E) in 3 (9%). No mutation was found in NRAS(Q61). BRAF(V600E) was associated with older age and larger tumor size (p < 0.05), and RET/PTC3 was associated with a larger tumor size and multifocality (p < 0.05). Conclusions: The genetic signature in this cohort was remarkably different than that observed in adults. Although observed at a lower prevalence, the spectrum of mutations was quite similar to that described in radiation-exposed pediatric PTCs. As mutations were unidentifiable in over 40% of the PTC cases, more comprehensive studies conducted in these patients will help to decipher the genetic landscape of sporadic pediatric PTCs. (AU)

• FAPESP's process: 13/03867-5 - Analysis of copy number variation (CNV) in pacientes of a family with men 2A and P.G533C mutation in the RET gene: identification of CNV regions associated with genesis and progression of medullary thyroid carcinoma
• Grantee: Janete Maria Cerutti
• Support Opportunities: Regular Research Grants