Analysis of oncogene and tumor suppressor gene alterations in pediatric malignant astrocytomas reveals reduced survival for patients with PTEN mutations

Corey Raffel, Lori Frederick, Judith R. O'Fallon, Pamela Atherton-Skaff, Arie Perry, Robert Brian Jenkins, C. David James

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Although common among adult intracranial neoplasms, pediatric malignant astrocytomas (PMAs) comprise a relatively small proportion of the brain tumors that occur in children. The scarcity of such cases generally requires that molecular analyses of PMAs are based on the utilization of paraffin- embedded material, and here we have used 39 such specimens to examine the incidence and prognostic significance of oncogene and tumor suppressor gene alterations (including amplifications of EGFR, CDK4, and MDM2 as well as inactivating mutations of CDKN2A, TP53, and PTEN) in these tumors. In general, the frequency of alteration for the genes we have studied fell within ranges that have been reported for adult astrocytomas. However, EGFR amplification, which is usually observed in approximately 40% and 15% of adult grade 4 and grade 3 astrocytomas, respectively, was not detected in any member of this series. With regard to prognosis, PTEN mutations were significantly associated with decreased survival among grade 3 and grade 4 PMA patients, a potentially important observation because neither patient age nor tumor malignancy grade was correlated with outcome for these individuals. In total, our data suggest at least one significant distinction between the genetic etiology of pediatric and adult astrocytomas and additionally reveal that analysis of PTEN mutations in PMA patients may be useful in the differential diagnosis of these tumors.

Original languageEnglish (US)
Pages (from-to)4085-4090
Number of pages6
JournalClinical Cancer Research
Volume5
Issue number12
StatePublished - Dec 1999

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Astrocytoma
Tumor Suppressor Genes
Oncogenes
Pediatrics
Mutation
Survival
Brain Neoplasms
Neoplasms
Gene Frequency
Paraffin
Differential Diagnosis
Observation
Incidence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Analysis of oncogene and tumor suppressor gene alterations in pediatric malignant astrocytomas reveals reduced survival for patients with PTEN mutations. / Raffel, Corey; Frederick, Lori; O'Fallon, Judith R.; Atherton-Skaff, Pamela; Perry, Arie; Jenkins, Robert Brian; James, C. David.

In: Clinical Cancer Research, Vol. 5, No. 12, 12.1999, p. 4085-4090.

Research output: Contribution to journalArticle

Raffel, Corey ; Frederick, Lori ; O'Fallon, Judith R. ; Atherton-Skaff, Pamela ; Perry, Arie ; Jenkins, Robert Brian ; James, C. David. / Analysis of oncogene and tumor suppressor gene alterations in pediatric malignant astrocytomas reveals reduced survival for patients with PTEN mutations. In: Clinical Cancer Research. 1999 ; Vol. 5, No. 12. pp. 4085-4090.
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