Prognostic Implications of Chromosome 17p Deletions in Human Medulloblastomas

J Neurooncol. 1995;24(1):39-45. doi: 10.1007/BF01052657.

Abstract

DNA derived from medulloblastoma biopsies was analyzed to determine if deletions of the 17p region, mutations of the TP53 gene, or amplification 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 samples, was associated with a shortened survival period (p = 0.045 by the logrank 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 tumors contained amplified N-myc, EGFR, or MDM2 genes. These results demonstrate that, while only rare medulloblastomas contain TP53 gene mutations or amplification of the c-myc gene, loss of heterozygosity on chromosome 17p is indicative of a significantly worse prognosis among patients with these tumors. Further, these results provide a strong impetus for a prospective analysis of loss of heterozygosity in a cooperative group setting, which would include tumor staging, a selection of treatment modalities, and multivariate analyses.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Cerebellar Neoplasms / genetics*
  • Cerebellar Neoplasms / mortality
  • Child
  • Child, Preschool
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 17*
  • DNA Probes
  • ErbB Receptors / genetics
  • Female
  • Genes, Tumor Suppressor
  • Genes, myc
  • Heterozygote*
  • Humans
  • Infant
  • Male
  • Medulloblastoma / genetics*
  • Medulloblastoma / mortality
  • Microsatellite Repeats
  • Point Mutation
  • Polymerase Chain Reaction
  • Prognosis

Substances

  • DNA Probes
  • ErbB Receptors