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Eric Y Lian
Eric Y Lian
Division of Cancer Biology and Genetics, Cancer Research Institute, Queen’s University, Kingston, Ontario, Canada
Department of Pathology & Molecular Medicine, Queen’s University, Kingston, Ontario, Canada
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Department of Pathology & Molecular Medicine, Queen’s University, Kingston, Ontario, Canada
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Sarah M Maritan
Sarah M Maritan
Division of Cancer Biology and Genetics, Cancer Research Institute, Queen’s University, Kingston, Ontario, Canada
Department of Pathology & Molecular Medicine, Queen’s University, Kingston, Ontario, Canada
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Department of Pathology & Molecular Medicine, Queen’s University, Kingston, Ontario, Canada
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Jessica G Cockburn
Jessica G Cockburn
Division of Cancer Biology and Genetics, Cancer Research Institute, Queen’s University, Kingston, Ontario, Canada
Department of Pathology & Molecular Medicine, Queen’s University, Kingston, Ontario, Canada
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Department of Pathology & Molecular Medicine, Queen’s University, Kingston, Ontario, Canada
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Katayoon Kasaian
Katayoon Kasaian
Michael Smith Genome Sciences Centre, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada
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Mathieu J F Crupi
Mathieu J F Crupi
Division of Cancer Biology and Genetics, Cancer Research Institute, Queen’s University, Kingston, Ontario, Canada
Department of Pathology & Molecular Medicine, Queen’s University, Kingston, Ontario, Canada
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Department of Pathology & Molecular Medicine, Queen’s University, Kingston, Ontario, Canada
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David Hurlbut
David Hurlbut
Department of Pathology & Molecular Medicine, Queen’s University, Kingston, Ontario, Canada
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Steven J M Jones
Steven J M Jones
Michael Smith Genome Sciences Centre, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada
Department of Medical Genetics, University of British Columbia, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada
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Department of Medical Genetics, University of British Columbia, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada
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Sam M Wiseman
Sam M Wiseman
Department of Surgery, St Paul’s Hospital & University of British Columbia, Vancouver, British Columbia, Canada
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Lois M Mulligan
Lois M Mulligan
Division of Cancer Biology and Genetics, Cancer Research Institute, Queen’s University, Kingston, Ontario, Canada
Department of Pathology & Molecular Medicine, Queen’s University, Kingston, Ontario, Canada
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Department of Pathology & Molecular Medicine, Queen’s University, Kingston, Ontario, Canada
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than those previously recognised. RET is expressed as two conserved protein isoforms, RET9 and RET51, generated by alternative splicing of 3′ exons ( Supplementary Fig. 1 , see section on supplementary data given at the end of this article), which
Maria Grazia Borrello
Maria Grazia Borrello
Operative Unit Molecular Mechanisms, Pathology and Laboratory Medicine, Unit of Medical Genetics, Scientific Directorate, Nuclear Medicine, Department of Experimental Oncology
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Antonella Aiello
Antonella Aiello
Operative Unit Molecular Mechanisms, Pathology and Laboratory Medicine, Unit of Medical Genetics, Scientific Directorate, Nuclear Medicine, Department of Experimental Oncology
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Bernard Peissel
Bernard Peissel
Operative Unit Molecular Mechanisms, Pathology and Laboratory Medicine, Unit of Medical Genetics, Scientific Directorate, Nuclear Medicine, Department of Experimental Oncology
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Maria Grazia Rizzetti
Maria Grazia Rizzetti
Operative Unit Molecular Mechanisms, Pathology and Laboratory Medicine, Unit of Medical Genetics, Scientific Directorate, Nuclear Medicine, Department of Experimental Oncology
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Piera Mondellini
Piera Mondellini
Operative Unit Molecular Mechanisms, Pathology and Laboratory Medicine, Unit of Medical Genetics, Scientific Directorate, Nuclear Medicine, Department of Experimental Oncology
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Debora Degl'Innocenti
Debora Degl'Innocenti
Operative Unit Molecular Mechanisms, Pathology and Laboratory Medicine, Unit of Medical Genetics, Scientific Directorate, Nuclear Medicine, Department of Experimental Oncology
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Veronica Catalano
Veronica Catalano
Operative Unit Molecular Mechanisms, Pathology and Laboratory Medicine, Unit of Medical Genetics, Scientific Directorate, Nuclear Medicine, Department of Experimental Oncology
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Morena Gobbo
Morena Gobbo
Operative Unit Molecular Mechanisms, Pathology and Laboratory Medicine, Unit of Medical Genetics, Scientific Directorate, Nuclear Medicine, Department of Experimental Oncology
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Paola Collini
Paola Collini
Operative Unit Molecular Mechanisms, Pathology and Laboratory Medicine, Unit of Medical Genetics, Scientific Directorate, Nuclear Medicine, Department of Experimental Oncology
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Italia Bongarzone
Italia Bongarzone
Operative Unit Molecular Mechanisms, Pathology and Laboratory Medicine, Unit of Medical Genetics, Scientific Directorate, Nuclear Medicine, Department of Experimental Oncology
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Marco A Pierotti
Marco A Pierotti
Operative Unit Molecular Mechanisms, Pathology and Laboratory Medicine, Unit of Medical Genetics, Scientific Directorate, Nuclear Medicine, Department of Experimental Oncology
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Angela Greco
Angela Greco
Operative Unit Molecular Mechanisms, Pathology and Laboratory Medicine, Unit of Medical Genetics, Scientific Directorate, Nuclear Medicine, Department of Experimental Oncology
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Ettore Seregni
Ettore Seregni
Operative Unit Molecular Mechanisms, Pathology and Laboratory Medicine, Unit of Medical Genetics, Scientific Directorate, Nuclear Medicine, Department of Experimental Oncology
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Introduction The RET (rearranged during transfection) gene encodes a tyrosine kinase receptor with a crucial role in development. RET comprises 21 exons and generates a transcript subjected to alternative splicing leading to two main isoforms: a
Tirtha K Das
Tirtha K Das
Department of Cell, Developmental and Regenerative Biology, School of Biomedical Sciences, Icahn School of Medicine, New York, New York, USA
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Ross L Cagan
Ross L Cagan
Department of Cell, Developmental and Regenerative Biology, School of Biomedical Sciences, Icahn School of Medicine, New York, New York, USA
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: genetic screens To model RET M918T (the RET isoform associated with MEN2B) Drosophila RET M955T was targeted to the developing eye, a well characterized epithelia in terms of cell–cell interactions and signal transduction ( Read et al . 2005 ). RET
Daniela Cordella
Daniela Cordella
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Marina Muzza
Marina Muzza
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Luisella Alberti
Luisella Alberti
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Paolo Colombo
Paolo Colombo
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Pietro Travaglini
Pietro Travaglini
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Paolo Beck-Peccoz
Paolo Beck-Peccoz
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Laura Fugazzola
Laura Fugazzola
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Luca Persani
Luca Persani
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approved by the ethics committees of the Institution. Functional studies Construction of the RET mutant Plasmids carrying Ret9-WT (the short isoform of protoRet gene) and Ret9-C634R (the short
Francesca Carlomagno
Francesca Carlomagno
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Teresa Guida
Teresa Guida
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Suresh Anaganti
Suresh Anaganti
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Livia Provitera
Livia Provitera
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Svend Kjaer
Svend Kjaer
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Structural Biology Laboratory, Cancer Discovery, c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, via S. Pansini 5, 80131 Naples, Italy
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Neil Q McDonald
Neil Q McDonald
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Structural Biology Laboratory, Cancer Discovery, c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, via S. Pansini 5, 80131 Naples, Italy
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Anderson J Ryan
Anderson J Ryan
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Structural Biology Laboratory, Cancer Discovery, c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, via S. Pansini 5, 80131 Naples, Italy
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Massimo Santoro
Massimo Santoro
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type . Japanese Journal of Cancer Research 90 1231 – 1237 . Vidal M Wells S Ryan A Cagan R 2005 ZD6474 suppresses oncogenic RET isoforms in a Drosophila model for type 2 multiple endocrine neoplasia syndromes and papillary thyroid
Hugo Prazeres
Hugo Prazeres
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) – Cancer Biology, Molecular Pathology Service, Endocrinology Service of the Portuguese Institute of Oncology of Coimbra FG, Department of Pathology, Rua Dr Roberto Frias, s/n, 4200-465 Porto, Portugal
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) – Cancer Biology, Molecular Pathology Service, Endocrinology Service of the Portuguese Institute of Oncology of Coimbra FG, Department of Pathology, Rua Dr Roberto Frias, s/n, 4200-465 Porto, Portugal
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) – Cancer Biology, Molecular Pathology Service, Endocrinology Service of the Portuguese Institute of Oncology of Coimbra FG, Department of Pathology, Rua Dr Roberto Frias, s/n, 4200-465 Porto, Portugal
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Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) – Cancer Biology, Molecular Pathology Service, Endocrinology Service of the Portuguese Institute of Oncology of Coimbra FG, Department of Pathology, Rua Dr Roberto Frias, s/n, 4200-465 Porto, Portugal
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) – Cancer Biology, Molecular Pathology Service, Endocrinology Service of the Portuguese Institute of Oncology of Coimbra FG, Department of Pathology, Rua Dr Roberto Frias, s/n, 4200-465 Porto, Portugal
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Joana P Couto
Joana P Couto
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) – Cancer Biology, Molecular Pathology Service, Endocrinology Service of the Portuguese Institute of Oncology of Coimbra FG, Department of Pathology, Rua Dr Roberto Frias, s/n, 4200-465 Porto, Portugal
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Fernando Rodrigues
Fernando Rodrigues
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) – Cancer Biology, Molecular Pathology Service, Endocrinology Service of the Portuguese Institute of Oncology of Coimbra FG, Department of Pathology, Rua Dr Roberto Frias, s/n, 4200-465 Porto, Portugal
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João Vinagre
João Vinagre
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) – Cancer Biology, Molecular Pathology Service, Endocrinology Service of the Portuguese Institute of Oncology of Coimbra FG, Department of Pathology, Rua Dr Roberto Frias, s/n, 4200-465 Porto, Portugal
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Joana Torres
Joana Torres
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) – Cancer Biology, Molecular Pathology Service, Endocrinology Service of the Portuguese Institute of Oncology of Coimbra FG, Department of Pathology, Rua Dr Roberto Frias, s/n, 4200-465 Porto, Portugal
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Vitor Trovisco
Vitor Trovisco
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) – Cancer Biology, Molecular Pathology Service, Endocrinology Service of the Portuguese Institute of Oncology of Coimbra FG, Department of Pathology, Rua Dr Roberto Frias, s/n, 4200-465 Porto, Portugal
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Teresa C Martins
Teresa C Martins
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) – Cancer Biology, Molecular Pathology Service, Endocrinology Service of the Portuguese Institute of Oncology of Coimbra FG, Department of Pathology, Rua Dr Roberto Frias, s/n, 4200-465 Porto, Portugal
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Manuel Sobrinho-Simões
Manuel Sobrinho-Simões
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) – Cancer Biology, Molecular Pathology Service, Endocrinology Service of the Portuguese Institute of Oncology of Coimbra FG, Department of Pathology, Rua Dr Roberto Frias, s/n, 4200-465 Porto, Portugal
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) – Cancer Biology, Molecular Pathology Service, Endocrinology Service of the Portuguese Institute of Oncology of Coimbra FG, Department of Pathology, Rua Dr Roberto Frias, s/n, 4200-465 Porto, Portugal
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Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) – Cancer Biology, Molecular Pathology Service, Endocrinology Service of the Portuguese Institute of Oncology of Coimbra FG, Department of Pathology, Rua Dr Roberto Frias, s/n, 4200-465 Porto, Portugal
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Paula Soares
Paula Soares
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) – Cancer Biology, Molecular Pathology Service, Endocrinology Service of the Portuguese Institute of Oncology of Coimbra FG, Department of Pathology, Rua Dr Roberto Frias, s/n, 4200-465 Porto, Portugal
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) – Cancer Biology, Molecular Pathology Service, Endocrinology Service of the Portuguese Institute of Oncology of Coimbra FG, Department of Pathology, Rua Dr Roberto Frias, s/n, 4200-465 Porto, Portugal
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Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) – Cancer Biology, Molecular Pathology Service, Endocrinology Service of the Portuguese Institute of Oncology of Coimbra FG, Department of Pathology, Rua Dr Roberto Frias, s/n, 4200-465 Porto, Portugal
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screening was performed in DNA obtained from peripheral blood leucocytes, by PCR amplification and direct Sanger sequencing of exons 8, 10, 11, and 13–16. Site-directed mutagenesis A pRcCMV vector expressing RET isoform 51 (i51) was mutated to generate the
Lois M Mulligan
Lois M Mulligan
Division of Cancer Biology and Genetics, Cancer Research Institute, Queen’s University, Kingston, Ontario, Canada
Department of Pathology and Molecular Medicine, Queen’s University, Kingston, Ontario, Canada
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Department of Pathology and Molecular Medicine, Queen’s University, Kingston, Ontario, Canada
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kinase domain is required for autophosphorylation and phosphorylation of substrates that promote RET downstream signals through multiple pathways ( Ibanez 2013 , Mulligan 2014 ). Finally, RET has two functionally distinct protein isoforms that differ in
Sara Redaelli
Sara Redaelli
School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
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Ivan Plaza-Menacho
Ivan Plaza-Menacho
Spanish National Cancer Research Center (CNIO), Madrid, Spain
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Luca Mologni
Luca Mologni
School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
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-1004(1999)13:4<331::AID-HUMU11>3.0.CO;2-# ) Vidal M Wells S Ryan A Cagan R 2005 ZD6474 suppresses oncogenic RET isoforms in a Drosophila model for type 2 multiple endocrine neoplasia syndromes and papillary thyroid carcinoma . Cancer Research 65 3538 – 3541
Barbora Bulanova Pekova
Barbora Bulanova Pekova
Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic
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Vlasta Sykorova
Vlasta Sykorova
Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic
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Karolina Mastnikova
Karolina Mastnikova
Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic
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Eliska Vaclavikova
Eliska Vaclavikova
Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic
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Jitka Moravcova
Jitka Moravcova
Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic
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Petr Vlcek
Petr Vlcek
Department of Nuclear Medicine and Endocrinology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
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Lucie Lancova
Lucie Lancova
Department of Nuclear Medicine and Endocrinology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
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Petr Lastuvka
Petr Lastuvka
Departments of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
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Rami Katra
Rami Katra
Department of Ear, Nose and Throat, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
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Petr Bavor
Petr Bavor
Department of Surgery, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
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Daniela Kodetova
Daniela Kodetova
Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
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Martin Chovanec
Martin Chovanec
Department of Otorhinolaryngology, 3rd Faculty of Medicine, University Hospital Kralovske Vinohrady, Prague, Czech Republic
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Jana Drozenova
Jana Drozenova
Department of Pathology, 3rd Faculty of Medicine, University Hospital Kralovske Vinohrady, Prague, Czech Republic
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Radoslav Matej
Radoslav Matej
Department of Pathology, 3rd Faculty of Medicine, University Hospital Kralovske Vinohrady, Prague, Czech Republic
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Jaromir Astl
Jaromir Astl
Department of Otorhinolaryngology and Maxillofacial Surgery, 3rd Faculty of Medicine and Military University Hospital, Prague, Czech Republic
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Jiri Hlozek
Jiri Hlozek
Department of Otorhinolaryngology and Maxillofacial Surgery, 3rd Faculty of Medicine and Military University Hospital, Prague, Czech Republic
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Petr Hrabal
Petr Hrabal
Department of Pathology, Military University Hospital, Prague, Czech Republic
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Josef Vcelak
Josef Vcelak
Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic
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Bela Bendlova
Bela Bendlova
Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic
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+ FBXO41/RET ). In some cases of CCDC6/RET and NCOA4/RET fusion genes, different isoforms were revealed (Supplementary Table 2). Figure 2 Overview of identified RET fusion genes. Partner genes were most frequently fused to exon 12 of the RET
Maria Domenica Castellone
Maria Domenica Castellone
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR ‘G. Salvatore’, Naples, Italy
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Rosa Marina Melillo
Rosa Marina Melillo
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR ‘G. Salvatore’, Naples, Italy
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, University of Naples ‘Federico II’, Naples, Italy
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Dipartimento di Medicina Molecolare e Biotecnologie Mediche, University of Naples ‘Federico II’, Naples, Italy
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2002 ). Three RET isoforms (RET9, RET43 and RET51) encoding for protein variants differing in the intracellular tyrosines involved in RET activation ( Tahira et al . 1990 , Lorenzo et al . 1995 , Matera et al . 2000 ) have been described. RET is
