Abstract
Various brain tumors are components of familial cancer syndromes, and Li-Fraumeni syndrome and Li-Fraumeni-like syndromes are the most famous entities. A rare, sporadic occurrence of brain tumor in peculiarly young subjects, however, sometimes provides a clue to understanding of carcinogenesis due to germline mutations. In this section, two cases of glial tumors in subjects having germline mutation of TP53 are presented, and genetic etiology of brain tumor is discussed. The first case is a 41 year-old father of a fatal adrenocortical carcinoma case of a 4-years-old daughter, 16 years prior to the occurrence of astrocytoma of himself. The search for family history and previous clinical records in the four different community hospitals for the last three decades and the follow-ups of his family members disclosed cancer of urinary bladder, cancer of pancreas, hepatoblastoma, and thymoma in the relatives. Germline mutation E286A of TP53 was identified in the affected members. Another case is a 21-year-old male, without any family history of cancer, who suffered from brain tumor and colorectal cancer. An attending physician was sticky to find an etiology in this unusual occurrence of cancer. After several attempts in vain, an I195T germline mutation was identified and functional analysis was performed. These anecdotes highlight importance of genetic analysis in case of glial tumors in relatively young adult or in adolescence whether or not they have family history of cancer. The problems and strategies to find TP53 mutation carriers and to prevent or to delay the occurrence of the tumors in them are discussed.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Achatz MI, Hainaut P, Ashton-Prolla P (2009) Highly prevalent TP53 mutation predisposing to many cancers in the Brazilian population: a case for newborn screening? Lancet Oncol 10:920–925
Bogler O, Huang HJ, Kleihues P, Cavenee WK (1995) The p53 gene and its role in human brain tumors. Gila 15:308–327
Burger PC, Scheithauer BW (2007) Tumor of the central nervous system, vol 7. American Registry of Pathology and Armed Forces Institute of Pathology, Washington, DC
Goi K, Takagi M, Iwata S, Delia D, Asada M, Donghi R, Tsunematsu Y, Nakazawa S, Yamamoto H, Yokota J, Tamura K, Saeki Y, Utsunomiya J, Takahashi T, Ueda R, Ishioka C, Eguchi M, Kamata N, Mizutani S (1997) DNA damage-associated dysregulation of the cell cycle and apoptosis control in cells with germ-line p53 mutation. Cancer Res 57:1895–1902
Hussain SP, Hollstein MH, Harris CC (2000) p53 tumor suppressor gene: at the crossroads of molecular carcinogenesis, molecular epidemiology, and human risk assessment. Ann NY Acad Sci 919:79–85
Jacks T, Remington L, Williams BO, Schmitt EM, Halachmi S, Bronson RT, Weinberg RA (1994) Tumor spectrum analysis in p53-mutant mice. Curr Biol 4:1–7
Jeannot E, Mellottee L, Bioulac-Sage P, Balabaud C, Scoazec JY, Van Nhieu JT, Bacq Y, Michalak S, Buob D, Genthep (Inserm network), Laurent-Puig P, Rusyn I, Zucman-Rossi J (2010) Spectrum of HNF1A somatic mutations in hepatocellular adenoma differs from that in MODY3 patients and suggests genotoxic damage. Diabetes. 59:1836–1844
Kahyo T, Ichikawa S, Hatanaka T, Yamada MK, Setou M (2008) A novel chalcone polyphenol inhibits the deacetylase activity of SIRT1 and cell growth in HEK293T cells. J Pharmacol Sci 108:364–371
Kleihues P, Schauble B, zur Hausen A, Esteve J, Ohgaki H (1997) Tumors associated with p53 germline mutations: a synopsis of 91 families. Am J Pathol 150:1–13
Kyritsis AP, Bondy ML, Xiao M, Berman EL, Cunningham JE, Lee PS, Levin VA, Saya H (1994) Germline p53 gene mutations in subsets of glioma patients. J Natl Cancer Inst 86:344–349
Ledford H (2010) Big science: the cancer genome challenge. Nature 464:972–974
Li FP, Fraumeni JF Jr, Mulvihill JJ, Blattner WA, Dreyfus MG, Tucker MA, Miller RA (1988) A cancer family syndrome in twenty-four kindreds. Cancer Res 48:5358–5362
Li YJ, Sanson M, Hoang-Xuan K, Delattre JY, Poisson M, Thomas G, Hamellin R (1995) Incidence of germ-line p53 mutations in patients with gliomas. Int J Cancer 64:383–387
Liu HK, Wang Y, Belz T, Bock D, Takacs A, Radlwimmer B, Barbus S, Reifenberger G, Lichter P, Schütz G (2010) The nuclear receptor tailless induces long-term neural stem cell expansion and brain tumor initiation. Genes Dev 24:683–695
Lubbe J, von Ammon K, Watanabe K, Hegi ME, Kleihues P (1995) Familial brain tumour syndrome associated with a p53 germline deletion of codon 236. Brain Pathol 5:15–23
Osborne RH, Houben MP, Tijssen CC, Coebergh JW, van Duijn CM (2001) The genetic epidemiology of glioma. Neurol 57:1751–1755
Palmero EI, Schuler-Faccini L, Caleffi M, Achatz MI, Olivier M, Martel-Planche G, Marcel V, Aguiar E, Giacomazzi J, Ewald IP, Giugliani R, Hainaut P, Ashton-Prolla P (2008) Detection of R337H, a germline TP53 mutation predisposing to multiple cancers, in asymptomatic women participating in a breast cancer screening program in Southern Brazil. Cancer Lett 261:21–25
Paraf F, Jothy S, Van Meir EG (1997) Brain tumor-polyposis syndrome: two genetic diseases? J Clin Oncol 15:2744–2758
Park DM, Yeaney GA, Hamilton RL, Mabold J, Urban N, Appleman L, Flickinger J, Lieberman F, Mintz A (2009) Identifying Muir-Torre syndrome in a patient with glioblastoma multiforme. Neuro Oncol 11:452–455
Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Kamiyama H, Jimeno A, Hong SM, Fu B, Lin MT, Calhoun ES, Kamiyama M, Walter K, Nikolskaya T, Nikolsky Y, Hartigan J, Smith DR, Hidalgo M, Leach SD, Klein AP, Jaffee EM, Goggins M, Maitra A, Iacobuzio-Donahue C, Eshleman JR, Kern SE, Hruban RH, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–1812
Paunu N, Syrjakoski K, Sankila R, Simola KO, Helen P, Niemela M, Matikainen M, Isola J, Haapasalo H (2001) Analysis of p53 tumor suppressor gene in families with multiple glioma patients. J Neurooncol 55:159–165
Pearson AD, Craft AW, Ratcliffe JM, Birch JM, Morris-Jones P, Roberts DF (1982) Two families with the Li-Fraumeni cancer family syndrome. J Med Genet 19:362–365
Petitjean A, Mathe E, Kato S, Ishioka C, Tavtigian SV, Hainaut P, Olivier M (2007) Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database. Hum Mutat 28:622–629
Portwine C, Chilton-MacNeill S, Brown C, Sexsmith E, McLaughlin J, Malkin D (2001) Absence of germline and somatic p53 alterations in children with sporadic brain tumors. J Neurooncol 52:227–235
Rieber J, Remke M, Hartmann C, Korshunov A, Burkhardt B, Sturm D, Mechtersheimer G, Wittmann A, Greil J, Blattmann C, Witt O, Behnisch W, Halatsch ME, Orakcioglu B, von Deimling A, Lichter P, Kulozik A, Pfister S (2009) Novel oncogene amplifications in tumors from a family with Li-Fraumeni syndrome. Genes Chromosomes Cancer 48:558–568
Sameshima Y, Tsunematsu Y, Watanabe S, Tsukamoto T, Kawa-ha K, Hirata Y, Mizoguchi H, Sugimura T, Terada M, Yokota J (1992) Detection of novel germ-line p53 mutations in diverse-cancer-prone families identified by selecting patients with childhood adrenocortical carcinoma. J Natl Cancer Inst 84:703–707
Santibanez-Koref MF, Birch JM, Hartley AL, Jones PH, Craft AW, Eden T, Crowther D, Kelsey AM, Harris M (1991) p53 germline mutations in Li-Fraumeni syndrome. Lancet 338:1490–1491
Schwartzbaum JA, Fisher JL, Aldape KD, Wrensch M (2006) Epidemiology and molecular pathology of glioma. Nat Clin Pract Neurol 2:494–503, quiz 491 p following 516
Schwarzbraun T, Obenauf AC, Langmann A, Gruber-Sedlmayr U, Wagner K, Speicher MR, Kroisel PM (2009) Predictive diagnosis of the cancer prone Li-Fraumeni syndrome by accident: new challenges through whole genome array testing. J Med Genet 46:341–344
Varley JM (2003) Germline TP53 mutations and Li-Fraumeni syndrome. Hum Mutat 21:313–320
Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller CR, Ding L, Golub T, Mesirov JP, Alexe G, Lawrence M, O’Kelly M, Tamayo P, Weir BA, Gabriel S, Winckler W, Gupta S, Jakkula L, Feiler HS, Hodgson JG, James CD, Sarkaria JN, Brennan C, Kahn A, Spellman PT, Wilson RK, Speed TP, Gray JW, Meyerson M, Getz G, Perou CM, Hayes DN, and Cancer Genome Atlas Research Network (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17:98–110
Vital A, Bringuier PP, Huang H, San Galli F, Rivel J, Ansoborlo S, Cazauran JM, Taillandier L, Kleihues P, Ohgaki H (1998) Astrocytomas and choroid plexus tumors in two families with identical p53 germline mutations. J Neuropathol Exp Neurol 57:1061–1069
Watanabe T, Vital A, Nobusawa S, Kleihues P, Ohgaki H (2009) Selective acquisition of IDH1 R132C mutations in astrocytomas associated with Li-Fraumeni syndrome. Acta Neuropathol 117:653–656
Yamada H, Shinmura K, Yamamura Y, Kurachi K, Nakamura T, Tsuneyoshi T, Yokota N, Maekawa M, Sugimura H (2009) Identification and characterization of a novel germline p53 mutation in a patient with glioblastoma and colon cancer. Int J Cancer 125:973–976
Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media B.V.
About this chapter
Cite this chapter
Sugimura, H. et al. (2011). Glioblastoma: Germline Mutation of TP53 . In: Hayat, M. (eds) Tumors of the Central Nervous System, Volume 2. Tumors of the Central Nervous System, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0618-7_4
Download citation
DOI: https://doi.org/10.1007/978-94-007-0618-7_4
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-0617-0
Online ISBN: 978-94-007-0618-7
eBook Packages: MedicineMedicine (R0)