TY - JOUR
T1 - Clinical and molecular characteristics of malignant transformation of low-grade glioma in children
AU - Broniscer, Alberto
AU - Baker, Suzanne J.
AU - West, Alina N.
AU - Fraser, Melissa M.
AU - Proko, Erika
AU - Kocak, Mehmet
AU - Dalton, James
AU - Zambetti, Gerard P.
AU - Ellison, David W.
AU - Kun, Larry E.
AU - Gajjar, Amar
AU - Gilbertson, Richard J.
AU - Fuller, Christine E.
PY - 2007/2/20
Y1 - 2007/2/20
N2 - Purpose: To analyze the clinical and molecular characteristics of malignant transformation (MT) of low-grade glioma (LGG) in children. Patients and 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. Conclusion: The molecular abnormalities that occur during MT of LGG in children are similar to those observed in primary and secondary glioblastoma in adults.
AB - Purpose: To analyze the clinical and molecular characteristics of malignant transformation (MT) of low-grade glioma (LGG) in children. Patients and 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. Conclusion: The molecular abnormalities that occur during MT of LGG in children are similar to those observed in primary and secondary glioblastoma in adults.
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U2 - 10.1200/JCO.2006.06.8213
DO - 10.1200/JCO.2006.06.8213
M3 - Article
C2 - 17308273
AN - SCOPUS:33947574174
SN - 0732-183X
VL - 25
SP - 682
EP - 689
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 6
ER -