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Molecular Biology and Genetics of Medulloblastoma

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Posterior Fossa Tumors in Children

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Abstract

Recent advances in molecular biology have led to the development of powerful tools for the study of medulloblastoma (MB) tumorigenesis, which have revealed new insights into the molecular and genetics basis of this disease. Throughout the life of an individual, the ~3 billion base pairs of DNA that constitute the human genome are exposed to mutagens and suffer errors in DNA replication; this assault leads to the acquisition of stable mutations through rounds of clonal selection and clonal expansion. The cancer genome, as a result of this process, is profoundly different from the genome that composes the constitutional DNA. The goal of cancer genomics is the study of the human cancer genome and the collection and description of all the alterations that make up for its divergence from the constitutional DNA. The mutations, inherited or acquired, contribute in different degrees to the development of cancer and its progression from a localized cancer to one that grows uncontrolled and then metastasizes. Recent studies based on high-throughput mutation detection techniques have shown that cancer genomes harbor from 10 to over 100 mutations. However, these studies are likely to underestimate the alterations caused by genomic rearrangements and copy number alterations (CNA); this suggests that the number of genes hit by somatic mutations is higher. Cell homeostasis can also be disrupted by mechanisms beyond the changes in DNA sequence; changes in DNA methylation status or histone acetylation can alter physiological cell processes like cell division. For this reason a comprehensive description of cancer genetics has to include studies at the level of the genome, epigenome, and transcriptome, as schematized in Fig. 1.

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Authors and Affiliations

  1. Department of Molecular Medicine and Medical Biotechnology, Federico II, University of Naples, Naples, Italy

    Pasquale De Antonellis M.D., Antonio Verrico M.D. & Massimo Zollo M.D.

  2. Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, ON, Canada

    Livia Garzia M.D. & Michael D. Taylor M.D.

  3. Department of Biochemistry and Medical Biotechnologies, Federico II, University of Naples, Naples, Italy

    Massimo Zollo M.D.

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  1. Pasquale De Antonellis M.D.
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  2. Livia Garzia M.D.
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  3. Antonio Verrico M.D.
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  4. Michael D. Taylor M.D.
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  5. Massimo Zollo M.D.
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  1. Neurosurgery, Acıbadem University, Istanbul, Istanbul, Turkey

    M. Memet Özek

  2. Pediatric Neurosurgery, Santobono Children's Hospital, Naples, Napoli, Italy

    Giuseppe Cinalli

  3. Dept. Neurosurgery, Royal Childrens Hospital, Melbourne, Victoria, Australia

    Wirginia Maixner

  4. Pediatric Neurosurgery, Hopital Necker-Enfants Malades, Paris, Paris, France

    Christian Sainte-Rose

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De Antonellis, P., Garzia, L., Verrico, A., Taylor, M.D., Zollo, M. (2015). Molecular Biology and Genetics of Medulloblastoma. In: Özek, M., Cinalli, G., Maixner, W., Sainte-Rose, C. (eds) Posterior Fossa Tumors in Children. Springer, Cham. https://doi.org/10.1007/978-3-319-11274-9_14

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