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 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.
Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA.
S K
SK
Batra
R E
RE
McLendon
J S
JS
Koo
S
S
Castelino-Prabhu
H E
HE
Fuchs
J P
JP
Krischer
H S
HS
Friedman
D D
DD
Bigner
S H
SH
Bigner
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D015342:DNA Probes; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D016147:Genes, Tumor Suppressor; D016259:Genes, myc; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000235:genetics* / Q000401:mortality; D018895:Microsatellite Repeats; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis
D015342:DNA Probes; D066246:ErbB Receptors