Only 1 - 2% of medulloblastomas are associated with a tumor syndrome.
The etiology remains unknown for the great majority of patients.
Tumor Syndromes associated with medulloblastoma:
Gorlin Syndrome
- Also called nevoid basal cell carcinoma (NBCC) syndrome.
- Autosomal dominant hereditary disorder.
- Loss of heterozygosity in the PCTH gene (a tumour suppressor gene).
- Multiple organ abnormalities affecting skin, skeletal system, genitourinary system, (ovarian fibromas) and central nervous system.
- As many as 5% of patients with nevoid basal cell carcinoma syndrome (NBCC) develop medulloblastoma (usually occur during the first 7 years of life).
- NBCC can also present with:
- basal cell carcinomas at a young age
- odontogenic keratocysts (benign cystic lesions of the jaw) between 10 and 30 years of age.
Naevoid basal cell carcinoma syndrome at the Atlas of Genetics and Cytogenetics in Oncology and Haematology.
Turcot syndrome
- Autosomal dominant hereditary cancer syndrome.
- Turcot syndrome is characterized by polyps of the colon (Familial adenomatous polyposis and Hereditary nonpolyposis colorectal cancer)
- Increased risk of brain tumors (medulloblastomas and gliomas)
- Medulloblastoma is most likely to occur in the first 2 decades of life.
Turcot syndrome at the Atlas of Genetics and Cytogenetics in Oncology and Haematology
Oncogenetics
- Most common genetic abnormality detected in medulloblastoma is the loss of chromosome 17p, yielding isochromosome 17q.
- This has led to the attempted isolation of a putative tumor suppressor gene, which has been narrowed to the vicinity of 17p13.
- As the p53 gene localizes to 17p13, it is now thought that medulloblastoma involves the alteration of the p53 gene or that another tumor suppressor gene on the arm of chromosome 17 is responsible for the disease.
- While chromosome 17p deletion is common to most forms of medulloblastoma, there are several molecular correlations with the prognosis of these tumors.
- Amplifications of MYC are apparent in tumors with double minutes, are related to anaplastic large cell tumors and a poor prognosis.
- Increased levels of Erb2 expression are also associated with a poorer outcome for the patient.
- Only 5% of medulloblastomas exhibit amplification of known oncogenes.
- The most common of these is c-myc.
- While medulloblastoma cell lines show c-myc amplification, it is not yet known whether this extends to tumors in vivo.
Contributing Factor |
Association with Brain Tumor development |
Hereditary Condition |
Nevoid basal cell carcinoma syndrome |
Oncogenetic factors |
Loss of chromosome 17p |
