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

Edward Pan, Malgorzata Pellarin, Emi Holmes, Ivan Smirnov, Anjan Misra, Charles G. Eberhart, Peter C. Burger, Jaclyn A. Biegel, Burt G. Feuerstein, Shaun Mason

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Abstract

Background: Medulloblastomas are the most common primary malignant childhood intracranial neoplasms. Patients are currently sorted into three risk groups based on clinical criteria: standard, poor, and infant (<18 months old). We hypothesized that genetic copy number aberrations (CNA) predict prognosis and would provide improved criteria for predicting outcome. Methods: DNA from 35 medulloblastoma patients from four Children's Cancer Group trials was analyzed by comparative genomic hybridization to determine CNAs. The genetic alterations were evaluated using statistical and cluster analyses. Rasults: The most frequent CNAs were gains on 17q, 7, 1q, and 7q and losses on 17p, 10q, X, 16q, and 11q. Amplification at 5p15.1-p15.3 was also detected. Isochromosome 17q (i(17)(q10)) was associated with poor overall survival (P = 0.03) and event-free survival (P = 0.04) independent of poor risk group classification. Age <3 tended to be associated with <3 CNAs (P = 0.06). Unsupervised cluster analysis sorted the study patients into four subgroups based on CNAs. Supervised analysis using the program Significance Analysis of Microarrays (SAM) quantitatively validated those CNAs identified by unsupervised clustering that significantly distinguished among the four subgroups. Conclusions: Medulloblastomas are genetically heterogeneous and can be categorized into separate genetic subgroups by their CNAs using unsupervised cluster analysis and SAM. i(17)(q10) was a significant independent negative prognostic factor. Infant medulloblastomas may be a distinct genetic subset from those of older patients.

Original languageEnglish (US)
Pages (from-to)4733-4740
Number of pages8
JournalClinical Cancer Research
Volume11
Issue number13
DOIs
StatePublished - Jul 1 2005

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Isochromosomes
Medulloblastoma
Cluster Analysis
Microarray Analysis
Comparative Genomic Hybridization
Brain Neoplasms
Disease-Free Survival
Survival
DNA
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Isochromosome 17q is a negative prognostic factor in poor-risk childhood medulloblastoma patients. / Pan, Edward; Pellarin, Malgorzata; Holmes, Emi; Smirnov, Ivan; Misra, Anjan; Eberhart, Charles G.; Burger, Peter C.; Biegel, Jaclyn A.; Feuerstein, Burt G.; Mason, Shaun.

In: Clinical Cancer Research, Vol. 11, No. 13, 01.07.2005, p. 4733-4740.

Research output: Contribution to journalArticle

Pan, E, Pellarin, M, Holmes, E, Smirnov, I, Misra, A, Eberhart, CG, Burger, PC, Biegel, JA, Feuerstein, BG & Mason, S 2005, 'Isochromosome 17q is a negative prognostic factor in poor-risk childhood medulloblastoma patients', Clinical Cancer Research, vol. 11, no. 13, pp. 4733-4740. https://doi.org/10.1158/1078-0432.CCR-04-0465
Pan, Edward ; Pellarin, Malgorzata ; Holmes, Emi ; Smirnov, Ivan ; Misra, Anjan ; Eberhart, Charles G. ; Burger, Peter C. ; Biegel, Jaclyn A. ; Feuerstein, Burt G. ; Mason, Shaun. / Isochromosome 17q is a negative prognostic factor in poor-risk childhood medulloblastoma patients. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 13. pp. 4733-4740.
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AU - Pan, Edward

AU - Pellarin, Malgorzata

AU - Holmes, Emi

AU - Smirnov, Ivan

AU - Misra, Anjan

AU - Eberhart, Charles G.

AU - Burger, Peter C.

AU - Biegel, Jaclyn A.

AU - Feuerstein, Burt G.

AU - Mason, Shaun

PY - 2005/7/1

Y1 - 2005/7/1

N2 - Background: Medulloblastomas are the most common primary malignant childhood intracranial neoplasms. Patients are currently sorted into three risk groups based on clinical criteria: standard, poor, and infant (<18 months old). We hypothesized that genetic copy number aberrations (CNA) predict prognosis and would provide improved criteria for predicting outcome. Methods: DNA from 35 medulloblastoma patients from four Children's Cancer Group trials was analyzed by comparative genomic hybridization to determine CNAs. The genetic alterations were evaluated using statistical and cluster analyses. Rasults: The most frequent CNAs were gains on 17q, 7, 1q, and 7q and losses on 17p, 10q, X, 16q, and 11q. Amplification at 5p15.1-p15.3 was also detected. Isochromosome 17q (i(17)(q10)) was associated with poor overall survival (P = 0.03) and event-free survival (P = 0.04) independent of poor risk group classification. Age <3 tended to be associated with <3 CNAs (P = 0.06). Unsupervised cluster analysis sorted the study patients into four subgroups based on CNAs. Supervised analysis using the program Significance Analysis of Microarrays (SAM) quantitatively validated those CNAs identified by unsupervised clustering that significantly distinguished among the four subgroups. Conclusions: Medulloblastomas are genetically heterogeneous and can be categorized into separate genetic subgroups by their CNAs using unsupervised cluster analysis and SAM. i(17)(q10) was a significant independent negative prognostic factor. Infant medulloblastomas may be a distinct genetic subset from those of older patients.

AB - Background: Medulloblastomas are the most common primary malignant childhood intracranial neoplasms. Patients are currently sorted into three risk groups based on clinical criteria: standard, poor, and infant (<18 months old). We hypothesized that genetic copy number aberrations (CNA) predict prognosis and would provide improved criteria for predicting outcome. Methods: DNA from 35 medulloblastoma patients from four Children's Cancer Group trials was analyzed by comparative genomic hybridization to determine CNAs. The genetic alterations were evaluated using statistical and cluster analyses. Rasults: The most frequent CNAs were gains on 17q, 7, 1q, and 7q and losses on 17p, 10q, X, 16q, and 11q. Amplification at 5p15.1-p15.3 was also detected. Isochromosome 17q (i(17)(q10)) was associated with poor overall survival (P = 0.03) and event-free survival (P = 0.04) independent of poor risk group classification. Age <3 tended to be associated with <3 CNAs (P = 0.06). Unsupervised cluster analysis sorted the study patients into four subgroups based on CNAs. Supervised analysis using the program Significance Analysis of Microarrays (SAM) quantitatively validated those CNAs identified by unsupervised clustering that significantly distinguished among the four subgroups. Conclusions: Medulloblastomas are genetically heterogeneous and can be categorized into separate genetic subgroups by their CNAs using unsupervised cluster analysis and SAM. i(17)(q10) was a significant independent negative prognostic factor. Infant medulloblastomas may be a distinct genetic subset from those of older patients.

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