title: AGK-BRAF gene fusion is a recurrent event in sporadic pediatric thyroid carcinoma.
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.
authors.affiliation: Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Maria Isabel C V
authors.initials: MI
authors.lastname: Cordioli
authors.affiliation: Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Lais
authors.initials: L
authors.lastname: Moraes
authors.affiliation: Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Gianna
authors.initials: G
authors.lastname: Carvalheira
authors.affiliation: Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Luiza
authors.initials: L
authors.lastname: Sisdelli
authors.affiliation: Department of Pathology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Maria Teresa S
authors.initials: MT
authors.lastname: Alves
authors.affiliation: Department of Pathology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Rosana
authors.initials: R
authors.lastname: Delcelo
authors.affiliation: Department of Pediatrics, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brazil.
authors.forename: Osmar
authors.initials: O
authors.lastname: Monte
authors.affiliation: Department of Pediatrics, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brazil.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Longui
authors.affiliation: Department of Medicine, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brazil.
authors.forename: Adriano N
authors.initials: AN
authors.lastname: Cury
authors.affiliation: Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Janete M
authors.initials: JM
authors.lastname: Cerutti
mesh_terms: D000293:Adolescent; D000091308:Angiopoietin-Like Protein 6; D000075802:Angiopoietin-like Proteins / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000235:genetics / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D008297:Male; D009154:Mutation; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*; D014178:Translocation, Genetic; D047368:Tumor Burden
chemical_list: C477601:ANGPTL6 protein, human; D000091308:Angiopoietin-Like Protein 6; D000075802:Angiopoietin-like Proteins; D015514:Oncogene Proteins, Fusion; D048493:Proto-Oncogene Proteins B-raf
keywords: AGK-BRAF; BRAF V600E; papillary thyroid carcinoma; pediatric thyroid cancer; sporadic thyroid carcinoma