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Cytogenetic and/or loss of heterozygosity studies were performed on 13 ependymomas, 11 pilocytic astrocytomas, and 18 oligodendrogliomas. Loss of chromosome 22 was the most frequent genetic abnormality among the ependymomas. We found no consistent genetic abnormality in pilocytic astrocytomas. The most common genetic abnormality in oligodendrogliomas was loss of a portion of chromosome 19. Each informative oligodendroglioma had loss of alleles mapped to the long arm (q) of chromosome 19. One oligodendroglioma had an apparent homozygous deletion of the D19S8 locus. Our results, when combined with those in the literature, indicate that chromosomes 9, 11, and 22 may harbor genes important for the pathogenesis of ependymomas and that 19q probably harbors a gene important for the pathogenesis of oligodendrogliomas.

The aims of this study were to correlate cytogenetic studies and molecular genetic loss of heterozygosity (LOH) analyses in human astrocytomas and mixed oligo-astrocytomas, and to locate putative tumor suppressor genes on chromosome 10. Paired blood and tumor samples from 53 patients were analyzed. The tumors included 45 diffuse astrocytomas (39 grade 4, 4 grade 3, and 2 grade 2), 1 astroblastoma, and 7 mixed oligo-astrocytomas (2 grade 4, 4 grade 3, and 1 grade 2). By cytogenetic analyses the most common numeric chromosome abnormalities were +7, -10, -13, -14, -17, +19, -22, and -Y. The most common structural abnormalities involved chromosome arms 1p, 1q, 5p, and 9p. By LOH and dosage analysis the most common molecular genetic abnormalities were of chromosome arms 5p, 6p, 7q, 9p, 10p, 10q, 13q, 14q, 17p, and 19p. When the results of all methods were combined, the most commonly abnormal chromosomes were, in descending frequency, 10, Y, 17, 7, 13, and 9. In 80 percent of cases the cytogenetic and molecular genetic studies were concordant. LOH studies were more sensitive in detecting loss of genetic material than cytogenetic analyses and accounted for 60% of the discordant results. When there were structural abnormalities, such as translocations or inversions, cytogenetic analysis was more sensitive in detecting an abnormality than molecular genetic studies. In addition to the 24 tumors which appeared to lose an entire copy of chromosome 10, there were 10 tumors with molecular genetic or cytogenetic evidence of loss of only a portion of chromosome 10. The genetic analyses of these tumors suggest that there are 2 regions on chromosome 10 that may contain potential tumor suppressor genes. One lies distal to locus D10S22 from 10q22 to 10qter, and the other lies proximal to locus TST1 on the 10q arm near the centromere or on the 10p arm.

BACKGROUND.Published karyotypes from aggressive (atypical and malignant) me-

Models describing progression in the genetic derangement of glial tumors have shown loss of chromosome 10 to occur most frequently in high-grade lesions, suggesting that identification of this loss may be prognostically significant. Fluorescence in situ hybridization (FISH) analysis may be a valuable adjunct to histological grading if it can accurately detect this loss. In this paper, the authors correlate results obtained from FISH, cytogenetic, molecular genetic, and flow cytometric analyses of a series of 39 brain specimens, including seven normal, two gliotic, and 30 neoplastic (one Grade II, one Grade III, and 28 Grade IV astrocytoma) specimens. Contiguous section of freshly resected surgical tissue were submitted for tissue culturing (karyotype) and touch preparation (FISH), snap-frozen (molecular genetic), or paraffin-embedded (histology and flow cytometry). Centromere-specific probes for chromosomes 10 and 12 were used for FISH analysis, and 19 restriction fragment length polymorphisms (two p-arm and 17 q-arm) and four microsatellite sequence polymorphisms (three p-arm and one q-arm) were used for molecular genetic analysis of chromosome 10. Findings showed FISH and loss of heterozygosity (LOH) analyses to be concordant in 33 of 38 specimens (sensitivity 94%, specificity 81%), with one specimen indeterminate on LOH analysis. Both FISH and LOH analyses were more sensitive at detecting chromosome 10 loss than conventional cytogenetic (karyotype) analysis. The authors conclude that FISH is a sensitive test for detecting chromosome 10 loss and ploidy in astrocytic tumors.