Real-time quantitative PCR analysis of gene dosages reveals gene amplification in low-grade oligodendrogliomas.
Proto-oncogene amplification is an important alteration that is present in about 45% to 50% of high-grade human gliomas. We studied this mechanism in 8 genes (cyclin-dependent kinase-4 [CDK4], MDM2, MDM4, renin-angiotensin system-1, ELF3, GAC1, human epidermal growth factor receptor-2, and platelet-derived growth factor receptor-A gene) in a series of 40 oligodendrogliomas (World Health Organization (WHO) grade II, 21; WHO grade III, 13; and WHO grade II-III oligoastrocytomas, 6) using real-time quantitative polymerase chain reaction. Amplification of at least 1 of these genes was detected in 58% of samples (23/40). By histopathologic grade, 67% of grade II oligodendrogliomas (14/21), 46% of grade III anaplastic oligodendrogliomas (6/13), and 50% of mixed oligoastrocytomas (3/6) were positive for amplification of at least 1 gene. CDK4, MDM2, and GAC1 were the most frequently involved genes (12/40 [30%], 12/40 [30%], and 13/40 [33%], respectively). Our findings demonstrate gene amplification in low-grade samples indicating that it is an important alteration in the early steps of oligodendroglioma development and, therefore, might be considered a molecular mechanism leading to malignant progression toward anaplastic forms.
Alonso
M Eva
ME
Department of Experimental Surgery, Molecular, Oncogenetics Laboratory, Research Unit, Hospital Universitario La Paz, Madrid, Spain.
Bello
M Josefa
MJ
Arjona
Dolores
D
Martinez-Glez
Victor
V
de Campos
Jose M
JM
Isla
Alberto
A
Kusak
Elena
E
Vaquero
Jesús
J
Gutierrez
Manuel
M
Sarasa
Jose L
JL
Rey
Juan A
JA
D014408:Biomarkers, Tumor / Q000032:analysis; D001932:Brain Neoplasms / Q000235:genetics*; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D009837:Oligodendroglioma / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas