AGK-BRAF gene fusion is a recurrent event in sporadic pediatric thyroid carcinoma

Author(s)

Cordioli, Maria Isabel C. V. ; Moraes, Lais ; Carvalheira, Gianna ; Sisdelli, Luiza ; Alves, Maria Teresa S. ; Delcelo, Rosana ; Monte, Osmar ; Longui, Carlos A. ; Cury, Adriano N. ; Cerutti, Janete M.

• Document type: Journal article
• Source: CANCER MEDICINE; v. 5, n. 7, p. 1535-1541, JUL 2016.
• Web of Science Citations: 10

Abstract

Thyroid cancer is the fastest increasing cancer worldwide in all age groups. Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer in both adults and children. PTC genomic landscape has been extensively studied in adults, but information regarding sporadic pediatric patients is lacking. Although BRAF V600E mutation is highly prevalent in adults, this mutation is uncommon in pediatric cases. As adult and pediatric PTC is a mitogen-activated protein kinase-driven cancer, this altered pathway might be activated by different genetic events. The aim of this study was to investigate the occurrence of AGK-BRAF fusion gene, recently described in radiation-exposed pediatric PTC, in a cohort of exclusively sporadic pediatric PTC. The series consisted of 30 pediatric PTC younger than 18 years of age at the time of diagnosis and 15 matched lymph node metastases (LNM). Primary tumors and matched LNM were screened for the presence of the AGK-BRAF fusion transcript by RT-PCR. To confirm the identity of the amplified products, randomly selected samples positive for the presence of the fusion transcripts were sequenced. Moreover, BRAF dual-color, break-apart probes confirmed BRAF rearrangement. Overall, the AGK-BRAF fusion gene was detected in 10% (3/30) of primary tumors. For one of these cases, paired LNM was also available, which also shows the presence of AGK-BRAF fusion gene. This study described, for the first time, the presence of AGK-BRAF in sporadic pediatric PTC. Understanding the molecular events underlying pediatric PTC may improve preoperative diagnosis, allow molecular prognostication and define a therapeutic approach toward sporadic PTC patients. (AU)

• FAPESP's process: 12/02902-9 - The role of microRNAs in the regulation of C1orf24 expression in thyroid tumors
• Grantee: Janete Maria Cerutti
• Support Opportunities: Regular Research Grants
• 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
• FAPESP's process: 14/06570-6 - Comprehensive whole exome, paired-end RNA and genome sequencing: new insights into genetic bases of thyroid carcinoma in pediatric and adult ages and applications in clinical practice
• Grantee: Janete Maria Cerutti
• Support Opportunities: Research Projects - Thematic Grants