title: The clinical phenotype of YWHAE-NUTM2B/E positive pediatric clear cell sarcoma of the kidney.
abstract: Clear cell sarcoma of the kidney (CCSK) although uncommon, is the second most frequent renal malignancy of childhood. Until now, the sole recurrent genetic aberration identified in CCSKs is t(10;17)(q22;p13), which gives rise to a fusion transcript of YWHAE and NUTM2B/E. So far, the clinical relevance of this fusion transcript is unknown. The aim of this descriptive study was to determine the clinical phenotype of t(10;17)(q22;p13) positive CCSKs. Snap-frozen tissues, formalin-fixed paraffin-embedded tissues or RNA previously extracted from CCSK samples throughout European, North-American and Japanese study groups were screened by RT-PCR for the YWHAE-NUTM2B/E transcript. Clinical characteristics, tumor characteristics, and outcome of patients with and without the fusion transcript were studied. The cohort comprised 51 previously published cases to which were added 139 internationally collected CCSK samples. RNA from 57 of these additionally collected cases was of sufficient quality to be successfully screened for the YWHAE-NUTM2B/E transcript. In total, seven of the 108 cases harbored the fusion transcript. Patients with tumors containing the fusion transcript were relatively young (median age 10 months), had associated low median tumor volumes and stage I disease was not observed in these patients. Two of seven patients relapsed and one of seven patients died of disease. Ranges of values were not overtly different between patients with and without the fusion transcript; however, the number of fusion transcript positive cases turned out to be too small to permit reliable statistical analysis. The current study did not identify an explicit clinical phenotype of CCSK cases harboring the YWHAE-NUTM2B/E fusion transcript.
authors.affiliation: Department of Oncology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.|Department of Pediatric Hematology and Oncology, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Saskia L
authors.initials: SL
authors.lastname: Gooskens
authors.affiliation: National Children's Research Center, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: Colin
authors.initials: C
authors.lastname: Kenny
authors.affiliation: National Children's Research Center, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lazaro
authors.affiliation: National Children's Research Center, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: Elaine
authors.initials: E
authors.lastname: O'Meara
authors.affiliation: Department of Statistics, Dutch Cancer Institute (NKI-AvL), Amsterdam, The Netherlands.
authors.forename: Harm
authors.initials: H
authors.lastname: van Tinteren
authors.affiliation: Department of Pediatric Hematology and Pediatric Onco-Hematology, Fondazione IRCCS Istituto Tumori, Milano, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Spreafico
authors.affiliation: Department of Pathology, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors.forename: Gordan
authors.initials: G
authors.lastname: Vujanic
authors.affiliation: Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University Schleswig-Holstein, Kiel, Germany.
authors.forename: Ivo
authors.initials: I
authors.lastname: Leuschner
authors.affiliation: Department of Pathology, Hopitaux Universitaires Est Parisien, Trousseau La Roche-Guyon, Paris, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Coulomb-L'Herminé
authors.affiliation: Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Perotti
authors.affiliation: Pediatric Hematology Oncology Program, Instituto Nacional Do Cancer, Rio De Janeiro, Brazil.
authors.forename: Beatriz
authors.initials: B
authors.lastname: de Camargo
authors.affiliation: Department of Pediatrics, Centre Lyon Berard, Lyon, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Bergeron
authors.affiliation: Department of Pediatric Oncology, Hospital Materno-Infantil, Malaga, Spain.
authors.forename: Tomas
authors.initials: T
authors.lastname: Acha García
authors.affiliation: Department of Diagnostic Pathology, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Mio
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Oncology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
authors.affiliation: Department of Pediatric Hematology and Oncology, Institute of Child Health, University College, London, UK.
authors.forename: Kathy
authors.initials: K
authors.lastname: Pritchard-Jones
authors.affiliation: Department of Pediatric Hematology/Oncology, University Hospital for Children, Homburg, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Graf
authors.affiliation: Department of Oncology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
authors.forename: Marry M
authors.initials: MM
authors.lastname: van den Heuvel-Eibrink
authors.affiliation: National Children's Research Center, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.|Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.|University of Dublin, Trinity College, Dublin, Ireland.
authors.forename: Maureen J
authors.initials: MJ
authors.lastname: O'Sullivan
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics*; D018227:Sarcoma, Clear Cell / Q000235:genetics / Q000473:pathology*; D016019:Survival Analysis
chemical_list: D048948:14-3-3 Proteins; D015514:Oncogene Proteins, Fusion; D012097:Repressor Proteins; C482983:YWHAE protein, human