Medulloblastoma Comprises Four Distinct Molecular Variants

DOI Web Site 被引用文献20件
  • Paul A. Northcott
    From the Hospital for Sick Children; University of Toronto, Toronto, Ontario, Canada; German Cancer Research Center; University of Heidelberg, Heidelberg, Germany; Johns Hopkins University, Baltimore, MD; Northern Institute for Cancer Research, Newcastle University, Newcastle, United Kingdom; and Erasmus University Medical Center, Rotterdam, the Netherlands.
  • Andrey Korshunov
    From the Hospital for Sick Children; University of Toronto, Toronto, Ontario, Canada; German Cancer Research Center; University of Heidelberg, Heidelberg, Germany; Johns Hopkins University, Baltimore, MD; Northern Institute for Cancer Research, Newcastle University, Newcastle, United Kingdom; and Erasmus University Medical Center, Rotterdam, the Netherlands.
  • Hendrik Witt
    From the Hospital for Sick Children; University of Toronto, Toronto, Ontario, Canada; German Cancer Research Center; University of Heidelberg, Heidelberg, Germany; Johns Hopkins University, Baltimore, MD; Northern Institute for Cancer Research, Newcastle University, Newcastle, United Kingdom; and Erasmus University Medical Center, Rotterdam, the Netherlands.
  • Thomas Hielscher
    From the Hospital for Sick Children; University of Toronto, Toronto, Ontario, Canada; German Cancer Research Center; University of Heidelberg, Heidelberg, Germany; Johns Hopkins University, Baltimore, MD; Northern Institute for Cancer Research, Newcastle University, Newcastle, United Kingdom; and Erasmus University Medical Center, Rotterdam, the Netherlands.
  • Charles G. Eberhart
    From the Hospital for Sick Children; University of Toronto, Toronto, Ontario, Canada; German Cancer Research Center; University of Heidelberg, Heidelberg, Germany; Johns Hopkins University, Baltimore, MD; Northern Institute for Cancer Research, Newcastle University, Newcastle, United Kingdom; and Erasmus University Medical Center, Rotterdam, the Netherlands.
  • Stephen Mack
    From the Hospital for Sick Children; University of Toronto, Toronto, Ontario, Canada; German Cancer Research Center; University of Heidelberg, Heidelberg, Germany; Johns Hopkins University, Baltimore, MD; Northern Institute for Cancer Research, Newcastle University, Newcastle, United Kingdom; and Erasmus University Medical Center, Rotterdam, the Netherlands.
  • Eric Bouffet
    From the Hospital for Sick Children; University of Toronto, Toronto, Ontario, Canada; German Cancer Research Center; University of Heidelberg, Heidelberg, Germany; Johns Hopkins University, Baltimore, MD; Northern Institute for Cancer Research, Newcastle University, Newcastle, United Kingdom; and Erasmus University Medical Center, Rotterdam, the Netherlands.
  • Steven C. Clifford
    From the Hospital for Sick Children; University of Toronto, Toronto, Ontario, Canada; German Cancer Research Center; University of Heidelberg, Heidelberg, Germany; Johns Hopkins University, Baltimore, MD; Northern Institute for Cancer Research, Newcastle University, Newcastle, United Kingdom; and Erasmus University Medical Center, Rotterdam, the Netherlands.
  • Cynthia E. Hawkins
    From the Hospital for Sick Children; University of Toronto, Toronto, Ontario, Canada; German Cancer Research Center; University of Heidelberg, Heidelberg, Germany; Johns Hopkins University, Baltimore, MD; Northern Institute for Cancer Research, Newcastle University, Newcastle, United Kingdom; and Erasmus University Medical Center, Rotterdam, the Netherlands.
  • Pim French
    From the Hospital for Sick Children; University of Toronto, Toronto, Ontario, Canada; German Cancer Research Center; University of Heidelberg, Heidelberg, Germany; Johns Hopkins University, Baltimore, MD; Northern Institute for Cancer Research, Newcastle University, Newcastle, United Kingdom; and Erasmus University Medical Center, Rotterdam, the Netherlands.
  • James T. Rutka
    From the Hospital for Sick Children; University of Toronto, Toronto, Ontario, Canada; German Cancer Research Center; University of Heidelberg, Heidelberg, Germany; Johns Hopkins University, Baltimore, MD; Northern Institute for Cancer Research, Newcastle University, Newcastle, United Kingdom; and Erasmus University Medical Center, Rotterdam, the Netherlands.
  • Stefan Pfister
    From the Hospital for Sick Children; University of Toronto, Toronto, Ontario, Canada; German Cancer Research Center; University of Heidelberg, Heidelberg, Germany; Johns Hopkins University, Baltimore, MD; Northern Institute for Cancer Research, Newcastle University, Newcastle, United Kingdom; and Erasmus University Medical Center, Rotterdam, the Netherlands.
  • Michael D. Taylor
    From the Hospital for Sick Children; University of Toronto, Toronto, Ontario, Canada; German Cancer Research Center; University of Heidelberg, Heidelberg, Germany; Johns Hopkins University, Baltimore, MD; Northern Institute for Cancer Research, Newcastle University, Newcastle, United Kingdom; and Erasmus University Medical Center, Rotterdam, the Netherlands.

説明

<jats:sec><jats:title>Purpose</jats:title><jats:p>Recent genomic approaches have suggested the existence of multiple distinct subtypes of medulloblastoma. We studied a large cohort of medulloblastomas to determine how many subgroups of the disease exist, how they differ, and the extent of overlap between subgroups.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We determined gene expression profiles and DNA copy number aberrations for 103 primary medulloblastomas. Bioinformatic tools were used for class discovery of medulloblastoma subgroups based on the most informative genes in the data set. Immunohistochemistry for subgroup-specific signature genes was used to determine subgroup affiliation for 294 nonoverlapping medulloblastomas on two independent tissue microarrays.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Multiple unsupervised analyses of transcriptional profiles identified the following four distinct, nonoverlapping molecular variants: WNT, SHH, group C, and group D. Supervised analysis of these four subgroups revealed significant subgroup-specific demographics, histology, metastatic status, and DNA copy number aberrations. Immunohistochemistry for DKK1 (WNT), SFRP1 (SHH), NPR3 (group C), and KCNA1 (group D) could reliably and uniquely classify formalin-fixed medulloblastomas in approximately 98% of patients. Group C patients (NPR3-positive tumors) exhibited a significantly diminished progression-free and overall survival irrespective of their metastatic status.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Our integrative genomics approach to a large cohort of medulloblastomas has identified four disparate subgroups with distinct demographics, clinical presentation, transcriptional profiles, genetic abnormalities, and clinical outcome. Medulloblastomas can be reliably assigned to subgroups through immunohistochemistry, thereby making medulloblastoma subclassification widely available. Future research on medulloblastoma and the development of clinical trials should take into consideration these four distinct types of medulloblastoma.</jats:p></jats:sec>

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