Nervous system: Medulloblastoma

Identity

ICD-Topo	C710-C714,C717-C719,C720-C725,C716
ICD-Morpho	9470/3
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	MYCN	NOTCH2	NTRK3	OTX2	PIWIL2	PRAME	PTCH2
	PTCH1	REST	SLIT2	SOX11	SOX4

Translocations implicated (Data extracted from papers in the Atlas)

External links

Mitelman database	Topo ( Central_nervous_system_(all_sites) ) - Morpho ( PNET ) - Mitelman database (CGAP - NCBI)
COSMIC	Histo = - Site = central_nervous_system (COSMIC)
arrayMap	Topo ( C71,C72) Morph ( 9470/3) - arrayMap (Zurich)
Other database	Tumor Portal - Broad Institute
Other database	cBioPortal: Medulloblastoma (Broad, Nature 2012)
Other database	cBioPortal: Medulloblastoma (ICGC, Nature 2012)
Other database	cBioPortal: Medulloblastoma (PCGP, Nature 2012)

Bibliography

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PMID 3604579

Structural chromosomal abnormalities in human medulloblastoma.

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PMID 3422050

Isochromosome 17q in primitive neuroectodermal tumors of the central nervous system.

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PMID 2487154

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PMID 2539324

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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.

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PMID 1900966

Detection of an i(17q) chromosome by fluorescent in situ hybridization with a chromosome 17 alpha satellite DNA probe.

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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)

Written	07-2000	Anne 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.

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URL : http://AtlasGeneticsOncology.org/Tumors/MedulloblastomaID5065.html

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indexed on : Tue Sep 23 17:33:57 CEST 2014

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