Clinical and molecular characteristics of malignant transformation of low-grade glioma in children

Alberto Broniscer, Suzanne J. Baker, Alina N. West, Melissa M. Fraser, Erika Proko, Mehmet Kocak, James Dalton, Gerard P. Zambetti, David W. Ellison, Larry E. Kun, Amar Gajjar, Richard J. Gilbertson, Christine E. Fuller

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)682-689
Number of pages8
JournalJournal of Clinical Oncology
Volume25
Issue number6
DOIs
StatePublished - Feb 20 2007

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Glioma
Astrocytoma
Glioblastoma
Incidence
Fluorescence In Situ Hybridization
Oncogenes
Neoplasms
Radiotherapy
Immunohistochemistry

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Broniscer, A., Baker, S. J., West, A. N., Fraser, M. M., Proko, E., Kocak, M., ... Fuller, C. E. (2007). Clinical and molecular characteristics of malignant transformation of low-grade glioma in children. Journal of Clinical Oncology, 25(6), 682-689. https://doi.org/10.1200/JCO.2006.06.8213

Clinical and molecular characteristics of malignant transformation of low-grade glioma in children. / Broniscer, Alberto; Baker, Suzanne J.; West, Alina N.; Fraser, Melissa M.; Proko, Erika; Kocak, Mehmet; Dalton, James; Zambetti, Gerard P.; Ellison, David W.; Kun, Larry E.; Gajjar, Amar; Gilbertson, Richard J.; Fuller, Christine E.

In: Journal of Clinical Oncology, Vol. 25, No. 6, 20.02.2007, p. 682-689.

Research output: Contribution to journalArticle

Broniscer, A, Baker, SJ, West, AN, Fraser, MM, Proko, E, Kocak, M, Dalton, J, Zambetti, GP, Ellison, DW, Kun, LE, Gajjar, A, Gilbertson, RJ & Fuller, CE 2007, 'Clinical and molecular characteristics of malignant transformation of low-grade glioma in children', Journal of Clinical Oncology, vol. 25, no. 6, pp. 682-689. https://doi.org/10.1200/JCO.2006.06.8213
Broniscer, Alberto ; Baker, Suzanne J. ; West, Alina N. ; Fraser, Melissa M. ; Proko, Erika ; Kocak, Mehmet ; Dalton, James ; Zambetti, Gerard P. ; Ellison, David W. ; Kun, Larry E. ; Gajjar, Amar ; Gilbertson, Richard J. ; Fuller, Christine E. / Clinical and molecular characteristics of malignant transformation of low-grade glioma in children. In: Journal of Clinical Oncology. 2007 ; Vol. 25, No. 6. pp. 682-689.
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abstract = "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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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.

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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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