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.
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.
Authors: Nicolas R Smoll; Oliver P Gautschi; Bawarjan Schatlo; Karl Schaller; Damien C Weber Journal: Neuro Oncol Date: 2012-07-06 Impact factor: 12.300
Authors: A Kerpel; M Yalon; M Soudack; J Chiang; A Gajjar; K E Nichols; Z Patay; S Shrot; C Hoffmann Journal: AJNR Am J Neuroradiol Date: 2020-04-30 Impact factor: 3.825
Authors: Matthew Mistry; Nataliya Zhukova; Daniele Merico; Patricia Rakopoulos; Rahul Krishnatry; Mary Shago; James Stavropoulos; Noa Alon; Jason D Pole; Peter N Ray; Vilma Navickiene; Joshua Mangerel; Marc Remke; Pawel Buczkowicz; Vijay Ramaswamy; Ana Guerreiro Stucklin; Martin Li; Edwin J Young; Cindy Zhang; Pedro Castelo-Branco; Doua Bakry; Suzanne Laughlin; Adam Shlien; Jennifer Chan; Keith L Ligon; James T Rutka; Peter B Dirks; Michael D Taylor; Mark Greenberg; David Malkin; Annie Huang; Eric Bouffet; Cynthia E Hawkins; Uri Tabori Journal: J Clin Oncol Date: 2015-02-09 Impact factor: 44.544
Authors: Barbara S Paugh; Chunxu Qu; Chris Jones; Zhaoli Liu; Martyna Adamowicz-Brice; Junyuan Zhang; Dorine A Bax; Beth Coyle; Jennifer Barrow; Darren Hargrave; James Lowe; Amar Gajjar; Wei Zhao; Alberto Broniscer; David W Ellison; Richard G Grundy; Suzanne J Baker Journal: J Clin Oncol Date: 2010-05-17 Impact factor: 44.544