MYCC and MYCN Oncogene Amplification in Medulloblastoma

Author:

Aldosari Naji1,Bigner Sandra H.1,Burger Peter C.1,Becker Laurence1,Kepner James L.1,Friedman Henry S.1,McLendon Roger E.1

Affiliation:

1. From the Departments of Pathology (Drs Aldosari, Bigner, and McLendon) and Pediatrics (Dr Friedman), Duke University Medical Center, Durham, NC; the Department of Pathology, Johns Hopkins Medical Center, Baltimore, Md (Dr Burger); Hospital for Sick Children, Toronto, Ontario (Dr Becker); and Children's Oncology Group Research Data Center, Gainesville, Fla (Dr Kepner)

Abstract

Abstract Context.—Brain tumors are the most common solid tumor in childhood, and medulloblastoma is the most common malignant brain tumor in this age group. Cytogenetic abnormalities that have been described in childhood medulloblastoma include loss of 17p, amplification of MYCC (c-myc), amplification of MYCN (N-myc), and isochromosome 17q. Data on these tumors indicate that the frequency of MYCC amplification is 5% to 10%. Fluorescence in situ hybridization is a powerful tool for investigating these features on archival material. Objectives.—To determine if intratumoral heterogeneity exists for MYCC and MYCN in medulloblastomas and if tumors with amplified MYCC or MYCN exhibit consistent histologic patterns. Design.—In this fluorescence in situ hybridization study, we investigated the frequency and prognostic significance of MYCC and MYCN amplification in 77 medulloblastomas derived from the Children's Oncology Group. Results.—MYCC amplification occurred in only 4 (5.2%) of 77 tumors. The 4 patients died of clinically aggressive neoplasms within 7 months of diagnosis. Similarly, 4 of 77 patients' tumors were found to exhibit MYCN amplification, but survival data are incomplete at present, therefore prognostic significance cannot be characterized. Conclusions.—These data establish the frequency of MYCC amplification in a large cohort of children with medulloblastoma and further suggest that MYCC amplification may be a marker of poor prognosis. Intratumoral heterogeneity was identified for these oncogenes in that 1 patient's tumor exhibited evidence of both MYCN and MYCC amplification, and this patient experienced a shortened survival time.

Publisher

Archives of Pathology and Laboratory Medicine

Subject

Medical Laboratory Technology,General Medicine,Pathology and Forensic Medicine

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