Localization of common deletion regions on 1p and 19q in human gliomas andtheir association with histological subtype

Allelic alterations of chromosomes 1 and 19 are frequent events in human di ffuse gliomas and have recently proven to be strong predictors of chemother apeutic response and prolonged survival in oligodendrogliomas (Cairncross c t al., 1998; Smith et al,, submitted), Using 115 human diffuse gliomas, we localized regions of common allelic loss on chromosomes 1 and 19 and assess ed the association of these deletion intervals with glioma histological sub types. Further, we evaluated the capacity of multiple modalities to detect these alterations, including loss of heterozygosity (LOH), fluorescence in situ hybridization (FISH), and comparative genomic hybridization (CGH), The correlation coefficients for detection of 1p and 19q alterations, respecti vely, between modalities were: 0.98 and 0.87 for LOH and FISH, 0.79 and 0.6 0 for LOH and CGH, and 0.79 and 0.53 for FISH and CGH, Minimal deletion reg ions were defined on 19q13.3 (D19S412-D19S596) and 1p (D1S468-D1S1612), Los s of the 1p36 region was found in 18% of astrocytomas (10/55) and in 73% (2 4/33) of oligodendrogliomas (P < 0.0001), and loss of the 19q13.3 region wa s found in 38% (21/55) of astrocytomas and 73% (24/33) of oligodendroglioma s (P = 0.0017), Loss of both regions was found in 11% (6/55) of astrocytoma s and in 63% (21/33) of oligodendrogliomas (P < 0.0001). All gliomas with L OH on either 1p or 19q demonstrated loss of the corresponding FISH probe, 1 p36 or 19q13.3, suggesting not only locations of putative tumor suppressor genes, but also a simple assay for assessment of 1p and 19q alterations as diagnostic and prognostic markers.