PROGNOSTIC IMPLICATIONS OF CHROMOSOME 17P DELETIONS IN HUMAN MEDULLOBLASTOMAS

DNA derived from medulloblastoma biopsies was analyzed to determine if deletions of the 17p region, mutations of the TP53 gene, or amplifica tion of the c-myc, N-myc, EGFR (epidermal growth factor receptor), or MDM2 (murine double-minute-2) genes was indicative of a poor prognosis . Loss of heterozygosity for 17p, observed in 8/28 (29%) paired sample s, was associated with a shortened survival period (p = 0.045 by the l ogrank test). TP53 mutations occurred in 2/46 (4.3%) tumor samples. c- myc Amplification was seen in 3/43 (6.9%) cases, while none of the tum ors contained amplified N-myc, EGFR, or MDM2 genes. These results demo nstrate that, while only rare medulloblastomas contain TP53 gene mutat ions or amplification of the c-myc gene, loss of heterozygosity on chr omosome 17p is indicative of a significantly worse prognosis among pat ients with these tumors. Further, these results provide a strong impet us for a prospective analysis of loss of heterozygosity in a cooperati ve group setting, which would include tumor staging, a selection of tr eatment modalities, and multivariate analyses.