title: Clinical and molecular characteristics of malignant transformation of low-grade glioma in children.
abstract: OBJECTIVE
  To analyze the clinical and molecular characteristics of malignant transformation (MT) of low-grade glioma (LGG) in children.
  
  
  METHODS
  The clinical, radiologic, and histologic characteristics of children treated at our institution who experienced MT of LGG were reviewed. Molecular alterations in these tumors were analyzed by fluorescent in situ hybridization, immunohistochemistry, and TP53 sequencing. Cumulative incidence estimate and risk factors for MT were determined for 65 patients with grade 2 astrocytoma treated at our institution during the study interval.
  
  
  RESULTS
  Eleven patients who experienced MT were identified (median age at diagnosis of LGG, 13.3 years). Initial diagnoses were grade 2 astrocytoma (n = 6) and other grade 1/2 gliomas (n = 5). The median latency of MT was 5.1 years. Histologic diagnoses after MT were glioblastoma (n = 7) and other high-grade gliomas (n = 4). The 15-year cumulative incidence estimate of MT among 65 patients with grade 2 astrocytoma was 6.7% +/- 3.9%; no risk factor analyzed, including radiotherapy, was associated with MT. Tissue was available for molecular analysis in all patients, including nine with samples obtained before and after MT. TP53 overexpression was more common after MT. Deletions of RB1 and/or CDKN2A were observed in 71% of LGGs and in 90% of tumors after MT. PTEN pathway abnormalities occurred in 76% of patients. One of five oncogenes analyzed (PDGFRA) was amplified in one patient.
  
  
  CONCLUSIONS
  The molecular abnormalities that occur during MT of LGG in children are similar to those observed in primary and secondary glioblastoma in adults.
authors.affiliation: Department of Oncology, St Jude Children's Research Hospital, Memphis, TN 38105, USA. alberto.broniscer@stjude.org
authors.forename: Alberto
authors.initials: A
authors.lastname: Broniscer
authors.forename: Suzanne J
authors.initials: SJ
authors.lastname: Baker
authors.forename: Alina N
authors.initials: AN
authors.lastname: West
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Fraser
authors.forename: Erika
authors.initials: E
authors.lastname: Proko
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kocak
authors.forename: James
authors.initials: J
authors.lastname: Dalton
authors.forename: Gerard P
authors.initials: GP
authors.lastname: Zambetti
authors.forename: David W
authors.initials: DW
authors.lastname: Ellison
authors.forename: Larry E
authors.initials: LE
authors.lastname: Kun
authors.forename: Amar
authors.initials: A
authors.lastname: Gajjar
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Gilbertson
authors.forename: Christine E
authors.initials: CE
authors.lastname: Fuller
mesh_terms: D001707:Biopsy, Needle; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D009367:Neoplasm Staging; D011336:Probability; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53