Alterations in the RB1 pathway in low-grade diffuse gliomas lacking common genetic alterations
| Autor: | Young-Ho, Kim, Joel, Lachuer, Michel, Mittelbronn, Werner, Paulus, Benjamin, Brokinkel, Kathy, Keyvani, Ulrich, Sure, Karsten, Wrede, Sumihito, Nobusawa, Yoichi, Nakazato, Yuko, Tanaka, Anne, Vital, Luigi, Mariani, Hiroko, Ohgaki |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Comparative Genomic Hybridization Brain Neoplasms Genes p16 Glioma Kaplan-Meier Estimate DNA Methylation Middle Aged Polymerase Chain Reaction Retinoblastoma Protein Young Adult Child Preschool Humans Female Child Promoter Regions Genetic neoplasms Research Articles Aged Cyclin-Dependent Kinase Inhibitor p15 Signal Transduction |
| Zdroj: | Brain Pathol |
| ISSN: | 1750-3639 |
| Popis: | We recently reported that the vast majority (90%) of low-grade diffuse gliomas (diffuse astrocytoma, oligoastrocytoma and oligodendroglioma) carry at least one of the following genetic alterations: IDH1/2 mutation, TP53 mutation or 1p/19q loss. Only 7% of cases were triple-negative (ie, lacking any of these alterations). In the present study, array comparative genomic hybridization (CGH) in 15 triple-negative WHO grade II gliomas (eight diffuse astrocytomas and seven oligodendrogliomas) showed loss at 9p21 (p14(ARF) , p15(INK4b) , p16(INK4a) loci) and 13q14-13q32 (containing the RB1 locus) in three and two cases, respectively. Further analyses in 31 triple-negative cases as well as a total of 160 non-triple-negative cases revealed that alterations in the RB1 pathway (homozygous deletion and promoter methylation of the p15(INK4b) , p16(INK4a) and RB1 genes) were significantly more frequent in triple-negative (26%) than in non-triple-negative cases (11%; P = 0.0371). Multivariate analysis after adjustment for age, histology and treatment showed that RB1 pathway alterations were significantly associated with unfavorable outcome for patients with low-grade diffuse glioma [hazard ratio, 3.024 (1.279-6.631); P = 0.0057]. These results suggest that a fraction of low-grade diffuse gliomas lacking common genetic alterations may develop through a distinct genetic pathway, which may include loss of cell-cycle control regulated by the RB1 pathway. |
| Databáze: | OpenAIRE |
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