Alterations in the RB1 pathway in low-grade diffuse gliomas lacking common genetic alterations

作者: Young-Ho Kim , Joel Lachuer , Michel Mittelbronn , Werner Paulus , Benjamin Brokinkel

DOI: 10.1111/J.1750-3639.2011.00492.X

关键词:

摘要: We recently reported that the vast majority (<90%) of low-grade diffuse gliomas (diffuse astrocytoma, oligoastrocytoma and oligodendroglioma) carry at least one following genetic alterations: IDH1/2 mutation, TP53 mutation or 1p/19q loss. Only 7% cases were triple-negative (ie, lacking any these alterations). In present study, array comparative genomic hybridization (CGH) in 15 WHO grade II (eight astrocytomas seven oligodendrogliomas) showed loss 9p21 (p14(ARF) , p15(INK4b) p16(INK4a) loci) 13q14-13q32 (containing RB1 locus) three two cases, respectively. Further analyses 31 as well a total 160 non-triple-negative revealed alterations pathway (homozygous deletion promoter methylation genes) significantly more frequent (26%) than (11%; P?=?0.0371). Multivariate analysis after adjustment for age, histology treatment associated with unfavorable outcome patients glioma [hazard ratio, 3.024 (1.279-6.631); P?=?0.0057]. These results suggest fraction common may develop through distinct pathway, which include cell-cycle control regulated by pathway.

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