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Nervous system: Medulloblastoma

Identity

Phylum Nervous system:CNS:NonGlioma:Embryonal tumor:Medulloblastoma

Clinics and Pathology

Disease Medulloblastomas are malignant invasive embryonal tumours of the cerebellum with a tendency to metastasize in the central nervous system (CNS). This tumor is more frequently found in children.
Epidemiology It represents 10 at 20 % of brain tumours and 30 % of tumours localized in posterior fossa; annual incidence is 0,5 per 100 000 children; peak of occurrence at 7 years.
 
Histological features of a typical medulloblastoma: Homer-Wright rosettes - Anne Marie Capodano.
Pathology Belongs to the primitive neurectodermal tumours (PNET): highly malignant embryonal tumours of the CNS with predominant neuronal differentiation.
Several variants medulloblastoma are recognized in the OMS classification :
  • Classic medulloblastoma composed of densely jacked round-cells with round to oval hyperchromatic nuclei.
  • Desmoplastic medulloblastoma represents a variant with abundant reticulin and collagen.
  • Large cell medulloblastoma is a rare variant composed of cells with large round nuclei.
    Immuno histo chemistry : Classic medulloblastoma is strongly immuno-reactive for Vimentin. Some tumours are immunoreactive for NSE, Synaptophysine and GSAP.
  • Treatment The treatment associates total surgical resection and radiotherapy or, according to the age, chemotherapy.
    Prognosis Survival without recurrence is 50 at 70 %; depends on the quality of surgical resection and on the presence of metastases at the time of diagnosis.

    Cytogenetics

    Cytogenetics
    Morphological
  • The most common specific abnormality in medulloblastomas, which is present in approximately 50 % of cases, is isochromosome 17q [i(17q)]. The breakpoint is in the proximal portion of p-arm at 17p11.2, so that the resultant structure is dicentric. In a few cases, partial or complete loss of 17p occurs through interstitial deletion, unbalanced translocation or monosomy 17.
  • Chromosome 1 is also involved in medulloblastomas. The most frequent abnormalities are unbalanced translocations, deletions and duplications. Rearrangements of chromosome 1 often result in trisomy 1q without loss of the p-arm.
  • Others less common chromosomal changes are: deletions of 6q, 9q, 10q, 11q, 11p and 16q, monosomy 22 and in rare cases double minutes.
  • i(17q) - R-banding.
    Cytogenetics Molecular
  • Isochromosome 17 q has been observed in interphase nuclei using fluorescence in situ hybridization. This technique is used in particular when only a few metaphases are obtained or when only normal diploid cells are obtained in culture.
  • Genes involved and Proteins

    Note
  • Studies on loss of heterozygosity (LOH) have confirmed loss of portions of 17p in 30-45 % of cases. Some studies showed a correlation between LOH for 17p and a poor response to therapy and shortened survival. Mutations of p53 gene located on 17p13 have been found in only 5-10 % of these tumors.
  • Expression of PAX5 and PAX6 mRNA was shown in 70 % of medulloblastomas. The precise mechanism by which these genes are involved remains unknown.
  • Inactivation of PTCH tumor suppressor gene occurs in a subset of medulloblastomas.

  • Other genes implicated (Data extracted from papers in the Atlas)

    Genes AXIN1 BAP1 CASP8 CCNB1 CD44 COL1A2 ERBB2 HIC1 IRS1 ITGA9
    MAPRE1 MIR135A1 MIR7-1 NOTCH2 NTRK3 OTX2 PIWIL2 PRAME PTCH2
    REST SLIT2 SOX11 SOX4

    Translocations implicated (Data extracted from papers in the Atlas)

    External links

    5220 Primitive neuroectodermal tumor/Medulloblastoma;PNET
    Mitelman databaseTopo ( Central_nervous_system_(all_sites) ) - Morpho ( PNET ) - Mitelman database (CGAP - NCBI)
    COSMICHisto = - Site = central_nervous_system (COSMIC)
    Other databaseTumor Portal - Broad Institute
    Other databasecBioPortal: Medulloblastoma (Broad, Nature 2012)
    Other databasecBioPortal: Medulloblastoma (ICGC, Nature 2012)
    Other databasecBioPortal: Medulloblastoma (PCGP, Nature 2012)

    Bibliography

    Differentiation in the medulloblastoma. A histological and immunohistochemical study.
    Burger PC, Grahmann FC, Bliestle A, Kleihues P
    Acta neuropathologica. 1987 ; 73 (2) : 115-123.
    PMID 3604579
     
    Structural chromosomal abnormalities in human medulloblastoma.
    Bigner SH, Mark J, Friedman HS, Biegel JA, Bigner DD
    Cancer genetics and cytogenetics. 1988 ; 30 (1) : 91-101.
    PMID 3422050
     
    Isochromosome 17q in primitive neuroectodermal tumors of the central nervous system.
    Biegel JA, Rorke LB, Packer RJ, Sutton LN, Schut L, Bonner K, Emanuel BS
    Genes, chromosomes & cancer. 1989 ; 1 (2) : 139-147.
    PMID 2487154
     
    Detection of 1q polysomy in interphase nuclei of human solid tumors with a biotinylated probe.
    Viegas-Pˆ©quignot E, Jeanpierre M, Dutrillaux AM, Gerbault-Seureau M, Muleris M, Dutrillaux B
    Human genetics. 1989 ; 81 (4) : 311-314.
    PMID 2539324
     
    Cytogenetics and molecular genetics of malignant gliomas and medulloblastoma.
    Bigner SH, Vogelstein B
    Brain pathology (Zurich, Switzerland). 1990 ; 1 (1) : 12-18.
    PMID 1669688
     
    Deletion mapping of the medulloblastoma locus on chromosome 17p.
    Cogen PH, Daneshvar L, Metzger AK, Edwards MS
    Genomics. 1990 ; 8 (2) : 279-285.
    PMID 1979050
     
    Desmoplastic versus classic medulloblastoma: comparison of DNA content, histopathology and differentiation.
    Giangaspero F, Chieco P, Ceccarelli C, Lisignoli G, Pozzuoli R, Gambacorta M, Rossi G, Burger PC
    Virchows Archiv. A, Pathological anatomy and histopathology. 1991 ; 418 (3) : 207-214.
    PMID 1900966
     
    Detection of an i(17q) chromosome by fluorescent in situ hybridization with a chromosome 17 alpha satellite DNA probe.
    Nakagawa H, Inazawa J, Misawa S, Tanaka S, Takashima T, Taniwaki M, Abe T, Kashima K
    Cancer genetics and cytogenetics. 1992 ; 62 (2) : 140-143.
    PMID 1394099
     
    Detection of i(17q) chromosome by fluorescent in situ hybridization (FISH) with interphase nuclei in medulloblastoma.
    Vagner-Capodano AM, Zattara-Cannoni H, Gambarelli D, Gentet JC, Genitori L, Lena G, Graziani N, Raybaud C, Choux M, Grisoli F
    Cancer genetics and cytogenetics. 1994 ; 78 (1) : 1-6.
    PMID 7987794
     
    Extensive genomic abnormalities in childhood medulloblastoma by comparative genomic hybridization.
    Reardon DA, Michalkiewicz E, Boyett JM, Sublett JE, Entrekin RE, Ragsdale ST, Valentine MB, Behm FG, Li H, Heideman RL, Kun LE, Shapiro DN, Look AT
    Cancer research. 1997 ; 57 (18) : 4042-4047.
    PMID 9307291
     
    Diagnostic markers in paediatric medulloblastoma: a Paediatric Oncology Group Study.
    McLendon RE, Friedman HS, Fuchs HE, Kun LE, Bigner SH
    Histopathology. 1999 ; 34 (2) : 154-162.
    PMID 10064395
     
    Molecular genetic studies of chromosome 11 and chromosome 22q DNA sequences in pediatric medulloblastomas.
    Lescop S, Lellouch-Tubiana A, Vassal G, Besnard-Guerin C
    Journal of neuro-oncology. 1999 ; 44 (2) : 119-127.
    PMID 10619495
     
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    Contributor(s)

    Written07-2000Anne Marie Capodano

    Citation

    This paper should be referenced as such :
    Capodano, AM
    Nervous system tumors: Medulloblastoma
    Atlas Genet Cytogenet Oncol Haematol. 2000;4(3):147-148.
    Free online version   Free pdf version   [Bibliographic record ]
    URL : http://AtlasGeneticsOncology.org/Tumors/MedulloblastomaID5065.html

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Wed Jul 30 16:03:22 CEST 2014


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