Clinical and molecular characteristics of malignant transformation of low-grade glioma in children.
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.
Broniscer
Alberto
A
Department of Oncology, St Jude Children's Research Hospital, Memphis, TN 38105, USA. alberto.broniscer@stjude.org
Baker
Suzanne J
SJ
West
Alina N
AN
Fraser
Melissa M
MM
Proko
Erika
E
Kocak
Mehmet
M
Dalton
James
J
Zambetti
Gerard P
GP
Ellison
David W
DW
Kun
Larry E
LE
Gajjar
Amar
A
Gilbertson
Richard J
RJ
Fuller
Christine E
CE
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*
D016159:Tumor Suppressor Protein p53