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Isochromosome 17q is a negative prognostic factor in poor-risk childhood medulloblastoma patients

Edward Pan1, Malgorzata Pellarin, Emi Holmes

  • 1University of California San Francisco, San Francisco, California, USA.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|July 8, 2005
PubMed

Insights

Copy number aberrations (CNAs) in medulloblastomas can predict patient outcomes. Isochromosome 17q (i(17)(q10)) is a negative prognostic factor, suggesting distinct genetic subgroups in infant medulloblastomas.

Area of Science:

  • Pediatric Oncology
  • Cancer Genomics
  • Neuro-oncology

Background:

  • Medulloblastomas are the most common malignant brain tumors in children.
  • Current risk stratification relies on clinical criteria (standard, poor, infant).
  • Genetic copy number aberrations (CNAs) may offer improved prognostic criteria.

Purpose of the Study:

  • To investigate if CNAs predict prognosis in childhood medulloblastomas.
  • To identify specific genetic alterations associated with patient outcomes.
  • To explore the potential for genetic subtyping of medulloblastomas.

Main Methods:

  • Comparative genomic hybridization (CGH) was used to analyze DNA from 35 medulloblastoma patients.
  • Statistical and cluster analyses were employed to evaluate genetic alterations.
  • Significance Analysis of Microarrays (SAM) was used for supervised analysis.

Main Results:

  • Frequent CNAs included gains on 17q, 7, 1q, 7q and losses on 17p, 10q, X, 16q, 11q.
  • Isochromosome 17q (i(17)(q10)) correlated with poor overall and event-free survival.
  • Unsupervised clustering identified four distinct patient subgroups based on CNAs.

Conclusions:

  • Medulloblastomas exhibit genetic heterogeneity, classifiable into subgroups by CNAs.
  • i(17)(q10) is a significant independent negative prognostic factor.
  • Infant medulloblastomas may represent a distinct genetic subtype.
Abstract

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