title: A novel RET/PTC variant detected in a pediatric patient with papillary thyroid cancer without ionization history.
abstract: Papillary thyroid carcinoma (PTC) is the most frequent type of thyroid cancer. Its development is often caused by the formation of RET/PTC fused genes. RET/PTC1 is the most prevalent form, where exon 1 of CCDC6 gene is fused with the intracellular portion of RET protooncogene starting with exon 12. We have discovered a novel RET/PTC1 variant which we have named RET/PTC1ex9 in metastatic PTC of 8-year-old boy. RET/PTC1ex9 detection was performed by real-time polymerase chain reaction with melting curve analysis and subsequent Sanger and next-generation sequencing. A fusion of exon 1 of CCDC6 with exon 9 of extracellular domain of RET followed by exon 12 of RET was revealed. This is the first RET/PTC variant among PTC cases that contain the extracellular part of RET. This observation could be probably explained by incorrect splicing of RET due to the somatic 32-bp deletion in exon-intron 11 boundary of RET.
authors.affiliation: Department of Molecular Endocrinology, Institute of Endocrinology, Prague 1, 11694, Czech Republic; Department of Biochemistry, Faculty of Science, Charles University, Prague 2, 12843, Czech Republic. Electronic address: thalkova@endo.cz.
authors.forename: Tereza
authors.initials: T
authors.lastname: Halkova
authors.affiliation: Department of Molecular Endocrinology, Institute of Endocrinology, Prague 1, 11694, Czech Republic.
authors.forename: Sarka
authors.initials: S
authors.lastname: Dvorakova
authors.affiliation: Department of Molecular Endocrinology, Institute of Endocrinology, Prague 1, 11694, Czech Republic; Department of Biochemistry, Faculty of Science, Charles University, Prague 2, 12843, Czech Republic.
authors.forename: Eliska
authors.initials: E
authors.lastname: Vaclavikova
authors.affiliation: Department of Molecular Endocrinology, Institute of Endocrinology, Prague 1, 11694, Czech Republic.
authors.forename: Vlasta
authors.initials: V
authors.lastname: Sykorova
authors.affiliation: Department of Molecular Endocrinology, Institute of Endocrinology, Prague 1, 11694, Czech Republic; Department of Biochemistry, Faculty of Science, Charles University, Prague 2, 12843, Czech Republic.
authors.forename: Josef
authors.initials: J
authors.lastname: Vcelak
authors.affiliation: Department of Nuclear Medicine and Endocrinology, 2nd Faculty of Medicine, Charles University and Faculty Hospital Motol, Prague 5, 15006, Czech Republic.
authors.forename: Pavla
authors.initials: P
authors.lastname: Sykorova
authors.affiliation: Department of Nuclear Medicine and Endocrinology, 2nd Faculty of Medicine, Charles University and Faculty Hospital Motol, Prague 5, 15006, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Vlcek
authors.affiliation: Institute of Inherited Metabolic Disorders, 1st Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague 2, 12808, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Reboun
authors.affiliation: Department of ENT, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague 5, 15006, Czech Republic.
authors.forename: Rami
authors.initials: R
authors.lastname: Katra
authors.affiliation: Departments of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague 5, Czech Republic.
authors.forename: Daniela
authors.initials: D
authors.lastname: Kodetova
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands.
authors.forename: Melanie
authors.initials: M
authors.lastname: Schrumpf
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: van Wezel
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Morreau
authors.affiliation: Department of Molecular Endocrinology, Institute of Endocrinology, Prague 1, 11694, Czech Republic.
authors.forename: Bela
authors.initials: B
authors.lastname: Bendlova
mesh_terms: D002277:Carcinoma / Q000235:genetics*; D002291:Carcinoma, Papillary; D002648:Child; D015321:Gene Rearrangement; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D000072079:Patched Receptors; D016133:Polymerase Chain Reaction; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D017422:Sequence Analysis, DNA; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: D015514:Oncogene Proteins, Fusion; D000072079:Patched Receptors; D011956:Receptors, Cell Surface; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human
keywords: Fused gene; Next-generation sequencing; Papillary thyroid cancer; RET gene; RET/PTC rearrangement; RET/PTC1ex9