BACKGROUND: Reports of genetic analyses on pediatric gliomas are few, and those tumors have been far less characterized than adult gliomas. OBJECTIVE: To characterize the genetic and biological features of pediatric gliomas. METHODS: We investigated 23 pediatric nonependymal, nonpilocytic gliomas for chromosomal copy number aberrations (CNAs) by comparative genomic hybridization (CGH), mutations of isocitrate dehydrogenase (IDH) genes by direct sequencing, and proliferative activity and expression of O-methylguanine-DNA methyltransferase (MGMT) by immunohistochemistry. RESULTS: The most frequent CNA was single-copy gain of chromosome 1q, with 10 of 20 successfully investigated tumors showing the abnormality (50%). Other CNAs detected by CGH included gain on 7q (+7q) in 6, +9q in 5, +17q in 5, and + 7p in 4 cases. Gain of entire chromosome 7 was rare (2 cases), and codeletion of 1p and 19q was not detected. Gain of 1q was significantly predictive for shorter progression-free survival (PFS) and overall survival (OS), and even more closely associated with poor clinical outcome than histological grade (P = .0009 for PFS, P = .003 for OS by 1q status; P = .004 for PFS, P = .035 for OS by high-grade vs low-grade). Gain of 1q was also significantly correlated with proliferative activity (P = .0002), and tumors with 1q gain showed a trend toward higher MGMT expression (P = .27). Mutation of IDH1 gene was detected in only 2 of 17 tumors successfully analyzed. CONCLUSION: Single copy gain of 1q is associated with biological features of pediatric gliomas, and is a negative prognostic marker in patients with those tumors.
BACKGROUND: Reports of genetic analyses on pediatric gliomas are few, and those tumors have been far less characterized than adult gliomas. OBJECTIVE: To characterize the genetic and biological features of pediatric gliomas. METHODS: We investigated 23 pediatric nonependymal, nonpilocytic gliomas for chromosomal copy number aberrations (CNAs) by comparative genomic hybridization (CGH), mutations of isocitrate dehydrogenase (IDH) genes by direct sequencing, and proliferative activity and expression of O-methylguanine-DNA methyltransferase (MGMT) by immunohistochemistry. RESULTS: The most frequent CNA was single-copy gain of chromosome 1q, with 10 of 20 successfully investigated tumors showing the abnormality (50%). Other CNAs detected by CGH included gain on 7q (+7q) in 6, +9q in 5, +17q in 5, and + 7p in 4 cases. Gain of entire chromosome 7 was rare (2 cases), and codeletion of 1p and 19q was not detected. Gain of 1q was significantly predictive for shorter progression-free survival (PFS) and overall survival (OS), and even more closely associated with poor clinical outcome than histological grade (P = .0009 for PFS, P = .003 for OS by 1q status; P = .004 for PFS, P = .035 for OS by high-grade vs low-grade). Gain of 1q was also significantly correlated with proliferative activity (P = .0002), and tumors with 1q gain showed a trend toward higher MGMT expression (P = .27). Mutation of IDH1 gene was detected in only 2 of 17 tumors successfully analyzed. CONCLUSION: Single copy gain of 1q is associated with biological features of pediatric gliomas, and is a negative prognostic marker in patients with those tumors.
Authors: Eric J Gratias; Jeffrey S Dome; Lawrence J Jennings; Yueh-Yun Chi; Jing Tian; James Anderson; Paul Grundy; Elizabeth A Mullen; James I Geller; Conrad V Fernandez; Elizabeth J Perlman Journal: J Clin Oncol Date: 2016-07-11 Impact factor: 44.544
Authors: Guillaume Bergthold; Pratiti Bandopadhayay; Wenya Linda Bi; Lori Ramkissoon; Charles Stiles; Rosalind A Segal; Rameen Beroukhim; Keith L Ligon; Jacques Grill; Mark W Kieran Journal: Biochim Biophys Acta Date: 2014-02-28