Rare inherited syndromes that to some extent explain familial
glioma include Turcot's syndrome,
Li-Fraumeni syndrome and
neurofibromatosis types I and II. The majority of families with
glioma do not meet the clinical criteria for any of these syndromes. In order to study the genetic origin of familial
glioma, tumour
DNA (n = 35) or blood samples (n = 8) were collected from 25 families. The
glioma tumours were tested for
microsatellite instability (MSI) with two markers, BAT25 and BAT26, since
glioma is associated with hereditary non-polyposis
colon cancer (HNPCC) in Turcot's syndrome. Furthermore, p53 was screened from blood
DNA (exons 2-11) with temporal temperature gradient electrophoresis (TTGE) since germline mutations in p53 are seen in
Li-Fraumeni syndrome. In
gliomas, there is a wide variety of somatic mutations, such as, for instance, in p53, the
epidermal growth factor receptor (EGFR) and p16. The tumour suppressor gene PTEN is also often somatically mutated in
glioma, therefore it is attractive as a candidate gene for germline mutations in familial
glioma. Blood
DNA was directly sequenced for mutations in PTEN exons 1-9. The analysis showed that no mutations were found in either of the studied tumour suppressor genes, and no MSI-positive tumours were found. A common polymorphism in p53 at
codon 72 (
arginine/
proline) was found in 6/8 of the patients. Apparently, mutation in the tested tumour suppressor genes or DNA mismatch repair genes does not explain the familial
glioma observed in these families.