Analysis of p53 tumor suppressor gene in families with multiple glioma patients

• Published in: Journal of neuro-oncology Vol. 55; no. 3; pp. 159 - 165
• Main Authors: PAUNU, Niina, SYRJÄKOSKI, Kirsi, SANKILA, Risto, SIMOLA, Kalle O. J, HELEN, Pauli, NIEMELÄ, Mika, MATIKAINEN, Mika, ISOLA, Jorma, HAAPASALO, Hannu
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer 01.12.2001; Springer Nature B.V
• Subjects: Adult; Aged; Biological and medical sciences; Central Nervous System Neoplasms - epidemiology; Central Nervous System Neoplasms - genetics; Child; Exons - genetics; Finland - epidemiology; Gene Expression Regulation, Neoplastic; Gene Frequency; Genes, p53; Germ-Line Mutation; Glioma - epidemiology; Glioma - genetics; Humans; Li-Fraumeni Syndrome - classification; Li-Fraumeni Syndrome - epidemiology; Li-Fraumeni Syndrome - genetics; Male; Medical sciences; Middle Aged; Neoplasm Proteins - analysis; Neoplasm Proteins - genetics; Neoplasms - epidemiology; Neoplasms - genetics; Neoplastic Syndromes, Hereditary - epidemiology; Neoplastic Syndromes, Hereditary - genetics; Neurology; Pedigree; Polymorphism, Genetic; Retrospective Studies; Sequence Analysis, DNA; Tumor Suppressor Protein p53 - analysis; Tumors of the nervous system. Phacomatoses; Finland; Human; Immunohistochemistry; Nervous system diseases; Multiple; Family study; Malignant tumor; Gene expression; Carcinogenesis; Genetic disease; Polymerase chain reaction; Pathology; TP53 Gene; Li Fraumeni syndrome; Glioma; Germ line; Central nervous system disease; Tumor; Familial cancer; Mutation; Molecular biology; Tumor suppressor gene
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1023/A:1013890022041

The high incidence of gliomas in Li-Fraumeni families and the high frequency of somatic p53 mutations in sporadic glial tumors have raised the possibility that germline p53 mutations could play an important role in familial aggregation of gliomas. In the present study, 18 families with two or more gliomas were screened for germline p53 mutation. The families were identified through questionnaires sent to 369 consecutive glioma patients operated at Tampere University Hospital during 1983-1994. In these families, a family history of cancer was verified through the Finnish Cancer Registry. Interestingly, the questionnaires reveled only 15 of 57 cancers (index gliomas excluded) retrieved through the Cancer Registry. None of the 18 families fufilled the criteria for classic Li-Fraumeni syndrome. Immunostaining analysis of p53 protein accumulation suggested that alterations of the p53 gene are as common in familial as in sporadic gliomas. Sequencing analysis of exons 4-10 of the p53 gene revealed no germline mutations in any of the 18 families. Thus, although occasional glioma families carrying germline p53 mutations have been identified in earlier studies, systematic evaluation of familial glioma patients suggests that the p53 gene is not a common susceptibility gene in case of familial gliomas. The p53 tumor suppressor gene seems to have a similar role in the tumorigenesis of most familial and sporadic gliomas.