title: Clinical features of ATRX or DAXX mutated neuroblastoma.
abstract: OBJECTIVE
  Previously, we reported that alternative lengthening of telomere (ALT) may be a biomarker for chemo-sensitivity and late recurrence in neuroblastoma (NBL). In this study, alterations of ATRX or DAXX, which both encode chromatin remodeling proteins in telomeric region, and their relationship to ALT were examined in NBLs.
  
  
  METHODS
  Our previous report on 121 NBLs revealed 11 NBLs with elongated telomeres by ALT. In these NBLs, ATRX or DAXX gene alterations were identified using next-generation sequencing and compared to clinical and other biological factors.
  
  
  RESULTS
  In 11 ALT cases, DAXX mutations were detected in one case, and ATRX alterations were detected in 10 cases. Except for one case, no DAXX or ATRX alterations were detected in 110 tumors with normal or shortened telomeres. MYCN amplification was not detected in ATRX altered tumors. In ALT cases, three infants showed ATRX deletions, and all seven cases detected after 18months of age showed poor prognosis.
  
  
  CONCLUSIONS
  In NBLs, ALT was caused by ATRX or DAXX alterations. ATRX altered cases without MYCN amplification detected at greater than 18months showed poor prognosis, suggesting that ATRX or DAXX alterations are a particular NBL subtype. Since these tumors showed chemo-resistance and late recurrence, complete resection in a surgical approach should be performed to improve patient prognosis.
authors.affiliation: Graduate School of Biomedical Science & Health, Hiroshima University, Hiroshima 734-8551 Japan; Department of Pediatric Surgery, Hiroshima University Hospital, Hiroshima 734-8551 Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Kurihara
authors.affiliation: Graduate School of Biomedical Science & Health, Hiroshima University, Hiroshima 734-8551 Japan; Department of Pediatric Surgery, Hiroshima University Hospital, Hiroshima 734-8551 Japan; Natural Science Center for Basic Research and Development (N-BARD), Hiroshima University, Hiroshima, Japan. Electronic address: eiso@hiroshima-u.ac.jp.
authors.forename: Eiso
authors.initials: E
authors.lastname: Hiyama
authors.affiliation: Graduate School of Biomedical Science & Health, Hiroshima University, Hiroshima 734-8551 Japan; Department of Pediatric Surgery, Hiroshima University Hospital, Hiroshima 734-8551 Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Onitake
authors.affiliation: Natural Science Center for Basic Research and Development (N-BARD), Hiroshima University, Hiroshima, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Yamaoka
authors.affiliation: Natural Science Center for Basic Research and Development (N-BARD), Hiroshima University, Hiroshima, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Hiyama
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D056970:Co-Repressor Proteins; D004265:DNA Helicases / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D018832:Molecular Chaperones; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D009447:Neuroblastoma / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D011379:Prognosis; D059505:Telomere Homeostasis; D000075924:X-linked Nuclear Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein
keywords: ALT; ATRX; DAXX; Mutation; Neuroblastoma; Prognosis; Telomere