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Microsatellite instability, PTEN and p53 germline mutations in glioma
families
Malmer B, Gronberg H, Andersson U, Jonsson BA, Henriksson R
Department of Radiation Science, Oncology, Umea University
Hospital, Sweden. beatrice.malmer@onkologi.umu.se
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.
PMID: 11669337, UI: 21525507
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11669337
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