medulloblastoma
MIM.155255
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Medulloblastoma is a highly malignant embryonal tumor of the cerebellum that accounts for 20%-25% of all intracranial pediatric tumors.
Molecular biology
somatic mutations in PTCH and PTCH2 genes
allelotyping
expression profiling: 14500378
Cytogenetics
The most frequent chromosomal rearrangement in medulloblastoma is isochromosome 17, or i(17q).
17p deletion (TP53, KCTD11)
CGH
Losses
- 1q23.3-q24.2 deletion (16320246)
- 2q13.12-q13.2 deletion (16320246)
- 3q loss
- 6q loss (6q25-qter deletion) (16320246)
- 8p loss (8p23.1 deletion) (16320246)
- 10q loss (10q25.1 deletion) (16320246)
- 12q13.12-q13.2 deletion (16320246)
- 16q loss
- 17p loss
- 20p loss
Gains
Amplifications
2p amplification (MYCN, DDX1)
MYC by 8q24 amplification (16%) (16320246)
10p11 amplification (16320246)
3q amplification (16320246)
Allelotyping (11857089)
| Region | LOH% | Genes |
| 1p32 | - | PTCH2 |
| 5q22 | - | APC |
| 7q | 58.3% | |
| 8p22-23.1 | 66.7% | - |
| 9q22.3 | - | PTCH1 |
| 10q24-q25 | ||
| 10q25.3-q26.1 | ||
| 11q24.1-qter | ||
| 16q | 58.3% | |
| 17p13.1-p12 | 58.3% | TP53 |
| 17q | 66.7% |
Gene inactivating mutations
| PTCH2 | 1p32 | MIM.603673 |
| APC | 5q21-5q22 | MIM.175100 |
| SUFU | 10q24-q25 | MIM.607035 |
| BRCA2 | 13q12.3 | MIM.600185 |
Gene activating mutations
| CTNNB1 | 3p22-p21.3 | MIM.116806 |
Differential diagnosis
atypical teratoid/rhabdoid tumor (ATRT)
Predispositions
Fanconi anemia (Fanconi syndrome)
- +/- BRCA2 biallelic mutations (14670928)
Reviews
Ferretti E, Smaele ED, Marcotullio LD, Screpanti I, Gulino A. Hedgehog checkpoints in medulloblastoma: the chromosome 17p deletion paradigm. Trends Mol Med. 2005 Dec;11(12):537-45. PMID: 16290230
References
Lo KC, Rossi MR, Burkhardt T, Pomeroy SL, Cowell JK. Overlay analysis of the oligonucleotide array gene expression profiles and copy number abnormalities as determined by array comparative genomic hybridization in medulloblastomas. Genes Chromosomes Cancer. 2007 Jan;46(1):53-66. PMID: 17044047
Mendrzyk F, Korshunov A, Toedt G, Schwarz F, Korn B, Joos S, Hochhaus A, Schoch C, Lichter P, Radlwimmer B. Isochromosome breakpoints on 17p in medulloblastoma are flanked by different classes of DNA sequence repeats. Genes Chromosomes Cancer. 2006 Apr;45(4):401-10. PMID: 16419060
Rossi MR, Conroy J, McQuaid D, Nowak NJ, Rutka JT, Cowell JK. Array CGH analysis of pediatric medulloblastomas. Genes Chromosomes Cancer. 2006 Mar;45(3):290-303. PMID: 16320246