Abstract
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 revealed only 15 of 57 cancers (index gliomas excluded) retrieved through the Cancer Registry. None of the 18 families fulfilled 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.
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CBTRUS 1996 Annual Report: Published by the Central Brain Tumor Registry of the United States, 1997
Louis DN, von Deimling A: Hereditary tumor syndromes of the nervous system: overview and rare syndromes. Brain Pathol 5: 145–151, 1995
Ikizler Y, van Meyel DJ, Ramsay DA, Abdallah GL, Allaster RM, Macdonald DR, Cavenee WK, Cairncross JG: Gliomas in families. Can J Neurol Sci. 19: 492–497, 1992
Dirven CM, Tuerlings J, Molenaar WM, Go KG, Louis DN: Glioblastoma multiforme in four siblings: a cytogenetic and molecular genetic study. J Neuro-Oncol 24: 251–258, 1995
Choi NW, Schuman LM, Gullen WH: Epidemiology of primary central nervous system neoplasms. II. Case-control study. Am J Epidemiol 91: 467–485, 1970
Farwell J, Flannery JT: Cancer in relatives of children with central-nervous-system neoplasms. N Engl J Med. 311: 749–753, 1984
Wrensch M, Lee M, Miike R, Newman B, Barger G, Davis R, Wiencke J, Neuhaus J: Familial and personal medical history of cancer and nervous system conditions among adults with glioma and controls. Am J Epidemiol 145: 581–593, 1997
Malmer B, Grönberg H, Bergenheim AT, Lenner P, Henriksson R: Familial aggregation of astrocytoma in northern Sweden: an epidemiological cohort study. Int J Cancer 81: 366–370, 1999
Hemminki K, Li X, Vaittinen P, Dong C: Cancers in the firstdegree relatives of children with brain tumours. Br J Cancer 83: 407–411, 2000
Kleihues P, Schauble B, zur Hausen A, Esteve J, Ohgaki H: Tumors associated with p53 germline mutations: a synopsis of 91 families. Am J Pathol 150: 1–13, 1997
Li FP, Fraumeni JF Jr.: Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Ann Intern Med. 71: 747–752, 1969
Birch JM, Hartley AL, Tricker KJ, Prosser J, Condie A, Kelsey AM, Harris M, Jones PH, Binchy A, Crowther D: Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li–Fraumeni families. Cancer Res. 54: 1298–1304, 1994
Li YJ, Sanson M, Hoang-Xuan K, Delattre JY, Poisson M, Thomas G, Hamelin R: Incidence of germ-line p53 mutations in patients with gliomas. Int J Cancer 64: 383–387, 1995
Kyritsis AP, Bondy ML, Xiao M, Berman EL, Cunningham JE, Lee PS, Levin VA, Saya H: Germline p53 gene mutations in subsets of glioma patients. J Natl Cancer Inst. 86: 344–349, 1994
Lübbe J, von Ammon K, Watanabe K, Hegi ME, Kleihues P: Familial brain tumour syndrome associated with a p53 germline deletion of codon 236. Brain Pathol. 5: 15–23, 1995
Saeki Y, Tamura K, Yamamoto Y, Hatada T, Furuyama J, Utsunomiya J: Germline p53 mutation at codon 133 in a cancer-prone family. J Mol Med. 75: 50–56, 1997
Vital A, Bringuier PP, Huang H, San Galli F, Rivel J, Ansoborlo S, Cazauran JM, Taillandier L, Kleihues P, Ohgaki H: Astrocytomas and choroid plexus tumors in two families with identical p53 germline mutations. J Neuropathol Exp Neurol 57: 1061–1069, 1998
Tachibana I, Smith JS, Sato K, Hosek SM, Kimmel DW, Jenkins RB: Investigation of germline PTEN, p53, p16(INK4A)/p14(ARF), and CDK4 alterations in familial glioma. Am J Med Genet 92: 136–141, 2000
van Meyel DJ, Ramsay DA, Chambers AF, Macdonald DR, Cairncross JG: Absence of hereditary mutations in exons 5 through 9 of the p53 gene and exon 24 of the neurofibromin gene in families with glioma. Ann Neurol 35: 120–122, 1994
Miettinen HE, Jarvinen TA, Kellner U, Kauraniemi P, Parwaresch R, Rantala I, Kalimo H, Paljarvi L, Isola J, Haapasalo H: High topoisomerase IIalpha expression associates with high proliferation rate and and poor prognosis in oligodendrogliomas. Neuropathol Appl Neurobiol. 26: 504–512, 2000
Sallinen PK, Haapasalo HK, Visakorpi T, Helen PT, Rantala IS, Isola JJ, Helin HJ: Prognostication of astrocytoma patient survival by Ki-67 (MIB-1),PCNA, and S-phase fraction using archival paraffin-embedded samples. J Pathol. 174: 275–282, 1994
Kyritsis AP, Xu R, Bondy ML, Levin VA, Bruner JM: Correlation of p53 immunoreactivity and sequencing in patients with glioma. Mol Carcinog 15: 1–4, 1996
Ara S, Lee PS, Hansen MF, Saya H: Codon 72 polymorphism of the TP53 gene. Nucleic Acids Res. 18: 4961, 1990
Graziani D, Romagnoli S, Cassani B, Alfano RM, Roncalli M, Coggi G: An Ava I polymorphism in the TP53 gene. Mol Cell Probes 13: 393–395, 1999
Varley JM, McGown G, Thorncroft M, Santibanez-Koref MF, Kelsey AM, Tricker KJ, Evans DG, Birch JM: Germ-line mutations of TP53 in Li–Fraumeni families: an extended study of 39 families. Cancer Res. 57: 3245–3252, 1997
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Paunu, N., Syrjäkoski, K., Sankila, R. et al. Analysis of p53 Tumor Suppressor Gene in Families with Multiple Glioma Patients. J Neurooncol 55, 159–165 (2001). https://doi.org/10.1023/A:1013890022041
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DOI: https://doi.org/10.1023/A:1013890022041