title: Identification of Three Novel Fusion Oncogenes, SQSTM1/NTRK3, AFAP1L2/RET, and PPFIBP2/RET, in Thyroid Cancers of Young Patients in Fukushima.
abstract: The BRAFV600Emutation is the most frequent genetic abnormality in adult papillary thyroid carcinomas (PTCs). On the other hand, various chromosomal rearrangements are more prevalent in childhood and adolescent PTCs. The aim of the present study was to identify novel rearrangements in PTCs from young patients.
  
  
  
  Among 63 postoperative specimens of childhood and adolescent PTCs, which had been discovered by the thyroid ultrasound screening program in Fukushima, nine samples without prevalent known oncogenes, BRAFV600E, RAS, RET/PTC1, RET/PTC3, and ETV6/NTRK3, were analyzed in the current study by quantitative real-time reverse transcription polymerase chain reaction to screen for novel fusion genes by comparing transcript expression between extracellular and kinase domains of ALK, NTRK1, NTRK3, and RET.
  
  
  
  Of the above nine samples, five samples were suspected to harbor a fusion, and using subsequent 5' rapid amplification of cDNA end (RACE), two already reported fusion oncogenes, STRN/ALK and TPR/NTRK1, and three novel fusions, SQSTM1/NTRK3, AFAP1L2/RET, and PPFIBP2/RET, were identified. Functional analyses of these three chimeric genes were performed, and their transforming abilities were confirmed through the activation of mitogen-activated protein kinase (MAPK).
  
  
  
  Three novel fusion oncogenes have been identified in young PTC patients in Fukushima, suggesting that rare fusions may be present among the cases negative for known oncogenes in this age group and that such rearrangements can play a significant role in thyroid carcinogenesis.
authors.affiliation: 1 Department of Radiation Medical Sciences, Atomic Bomb Disease Institute , Nagasaki University, Nagasaki, Japan .|2 Nagasaki University Graduate School of Biomedical Sciences , Nagasaki, Japan .
authors.forename: Keita
authors.initials: K
authors.lastname: Iyama
authors.affiliation: 1 Department of Radiation Medical Sciences, Atomic Bomb Disease Institute , Nagasaki University, Nagasaki, Japan .
authors.forename: Michiko
authors.initials: M
authors.lastname: Matsuse
authors.affiliation: 1 Department of Radiation Medical Sciences, Atomic Bomb Disease Institute , Nagasaki University, Nagasaki, Japan .
authors.forename: Norisato
authors.initials: N
authors.lastname: Mitsutake
authors.affiliation: 1 Department of Radiation Medical Sciences, Atomic Bomb Disease Institute , Nagasaki University, Nagasaki, Japan .
authors.forename: Tatiana
authors.initials: T
authors.lastname: Rogounovitch
authors.affiliation: 3 Department of Radiation Molecular Epidemiology, Atomic Bomb Disease Institute , Nagasaki University, Nagasaki, Japan .
authors.forename: Vladimir
authors.initials: V
authors.lastname: Saenko
authors.affiliation: 1 Department of Radiation Medical Sciences, Atomic Bomb Disease Institute , Nagasaki University, Nagasaki, Japan .
authors.forename: Keiji
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: 4 Department of Thyroid and Endocrinology, Fukushima Medical University , Fukushima, Japan .
authors.forename: Mai
authors.initials: M
authors.lastname: Ashizawa
authors.affiliation: 4 Department of Thyroid and Endocrinology, Fukushima Medical University , Fukushima, Japan .
authors.forename: Chiyo
authors.initials: C
authors.lastname: Ookouchi
authors.affiliation: 4 Department of Thyroid and Endocrinology, Fukushima Medical University , Fukushima, Japan .
authors.forename: Satoshi
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: 4 Department of Thyroid and Endocrinology, Fukushima Medical University , Fukushima, Japan .
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mizunuma
authors.affiliation: 4 Department of Thyroid and Endocrinology, Fukushima Medical University , Fukushima, Japan .
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Fukushima
authors.affiliation: 4 Department of Thyroid and Endocrinology, Fukushima Medical University , Fukushima, Japan .
authors.forename: Shinichi
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: 1 Department of Radiation Medical Sciences, Atomic Bomb Disease Institute , Nagasaki University, Nagasaki, Japan .|3 Department of Radiation Molecular Epidemiology, Atomic Bomb Disease Institute , Nagasaki University, Nagasaki, Japan .
authors.forename: Shunichi
authors.initials: S
authors.lastname: Yamashita
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000818:Animals; D002277:Carcinoma / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D005260:Female; D062406:Fukushima Nuclear Accident; D015321:Gene Rearrangement; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007564:Japan; D020935:MAP Kinase Signaling System; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D041681:NIH 3T3 Cells; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D020812:Receptor, trkC / Q000235:genetics; D000071456:Sequestosome-1 Protein / Q000235:genetics; D013964:Thyroid Neoplasms / Q000209:etiology / Q000235:genetics*; D055815:Young Adult
chemical_list: C521126:AFAP1L2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D015514:Oncogene Proteins, Fusion; C559265:PPFIBP2 protein, human; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D020812:Receptor, trkC
keywords: NTRK3; RET; fusion gene; oncogene; papillary thyroid carcinoma; rearrangement