Abstract
Brain tumors are the second most common cause of cancer in children and the leading cause of morbidity and mortality. A significant number of these cancers have specific genetic events which could be traced to the germline. As a result, these cancer predisposition syndromes are seen in children with brain tumors in much higher frequency than other childhood cancers. These syndromes predispose the individual and family members to multiple cancers in different organs and to other manifestations caused by genetic dysfunction. Although these syndromes are devastating to the child and other family members from emotional and social reasons, recent genetic discoveries and careful observation and surveillance resulted in improved survival, reduced morbidity, and targeted therapies to these children. Therefore, high index of suspicion and early referral to genetic testing and counseling is an important part of the treatment plan and may offer hope to these families. This chapter will discuss the clinical manifestations, genetic overview, and management of these complex syndromes.
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References
Strahm B, Malkin D. Hereditary cancer predisposition in children: genetic basis and clinical implications. Int J Cancer. 2006;119:2001–6.
Asthagiri AR, Parry DM, Butman JA, et al. Neurofibromatosis type 2. Lancet. 2009;373:1974–86.
Jett K, Friedman JM. Clinical and genetic aspects of neurofibromatosis 1. Genet Med. 2010;12:1–11.
Rubin JB, Gutmann DH. Neurofibromatosis type 1—a model for nervous system tumour formation? Nat Rev Cancer. 2005;5:557–64.
Tischkowitz M, Rosser E. Inherited cancer in children: practical/ethical problems and challenges. Eur J Cancer. 2004;40:2459–70.
Segal L, Darvish-Zargar M, Dilenge ME, et al. Optic pathway gliomas in patients with neurofibromatosis type 1: follow-up of 44 patients. J AAPOS. 2010;14:155–8.
Sharif S, Ferner R, Birch JM, et al. Second primary tumors in neurofibromatosis 1 patients treated for optic glioma: substantial risks after radiotherapy. J Clin Oncol. 2006;24:2570–5.
Ullrich NJ, Raja AI, Irons MB, et al. Brainstem lesions in neurofibromatosis type 1. Neurosurgery. 2007;61:762–6; discussion 766–7.
Rodriguez EF, Scheithauer BW, Giannini C, et al. PI3K/AKT pathway alterations are associated with clinically aggressive and histologically anaplastic subsets of pilocytic astrocytoma. Acta Neuropathol. 2011;121:407–20.
Krueger DA, Care MM, Holland K, et al. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med. 2010;363:1801–11.
Bree AF, Shah MR. Consensus statement from the first international colloquium on basal cell nevus syndrome (BCNS). Am J Med Genet A. 2011;155A:2091–7.
Lo Muzio L. Nevoid basal cell carcinoma syndrome (Gorlin syndrome). Orphanet J Rare Dis. 2008;3:32.
Brugieres L, Remenieras A, Pierron G, et al. High frequency of germline SUFU mutations in children with desmoplastic/nodular medulloblastoma younger than 3 years of age. J Clin Oncol. 2012;30:2087–93.
Taylor MD, Northcott PA, Korshunov A, et al. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol. 2012;123:465–72.
Rudin CM, Hann CL, Laterra J, et al. Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449. N Engl J Med. 2009;361:1173–8.
Robinson S, Cohen AR. Cowden disease and Lhermitte-Duclos disease: an update. Case report and review of the literature. Neurosurg Focus. 2006;20:E6.
Blumenthal GM, Dennis PA. PTEN hamartoma tumor syndromes. Eur J Hum Genet. 2008;16:1289–300.
Alter BP, Rosenberg PS, Brody LC. Clinical and molecular features associated with biallelic mutations in FANCD1/BRCA2. J Med Genet. 2007;44:1–9.
Reid S, Schindler D, Hanenberg H, et al. Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer. Nat Genet. 2007;39:162–4.
Kohlmann W, Gruber SB. Lynch syndrome. In: Pagon RA, Bird TD, Dolan CR, et al., editors. GeneReviews. Seattle: University of Washington; 2004.
Jasperson KW, Burt RW. APC-associated polyposis conditions. In: Pagon RA, Bird TD, Dolan CR, et al., editors. GeneReviews. Seattle: University of Washington, Seattle; 1998.
Evans DG, Baser ME, O’Reilly B, et al. Management of the patient and family with neurofibromatosis 2: a consensus conference statement. Br J Neurosurg. 2005;19:5–12.
Plotkin SR, Stemmer-Rachamimov AO, Barker II FG, et al. Hearing improvement after bevacizumab in patients with neurofibromatosis type 2. N Engl J Med. 2009;361:358–67.
Karajannis MA, Legault G, Hagiwara M, et al. Phase II trial of lapatinib in adult and pediatric patients with neurofibromatosis type 2 and progressive vestibular schwannomas. Neuro Oncol. 2012;14:1163–70.
Plotkin SR, Blakeley JO, Evans DG, et al. Update from the 2011 International Schwannomatosis Workshop: from genetics to diagnostic criteria. Am J Med Genet A. 2013;161:405–16.
Sestini R, Bacci C, Provenzano A, et al. Evidence of a four-hit mechanism involving SMARCB1 and NF2 in schwannomatosis-associated schwannomas. Hum Mutat. 2008;29:227–31.
Anderson J. Malignant rhabdoid tumors: a familial condition? Pediatr Blood Cancer. 2011;56:1–2.
Versteege I, Sevenet N, Lange J, et al. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature. 1998;394:203–6.
Chi SN, Zimmerman MA, Yao X, et al. Intensive multimodality treatment for children with newly diagnosed CNS atypical teratoid rhabdoid tumor. J Clin Oncol. 2009;27:385–9.
Hilden JM, Meerbaum S, Burger P, et al. Central nervous system atypical teratoid/rhabdoid tumor: results of therapy in children enrolled in a registry. J Clin Oncol. 2004;22:2877–84.
Tekautz TM, Fuller CE, Blaney S, et al. Atypical teratoid/rhabdoid tumors (ATRT): improved survival in children 3 years of age and older with radiation therapy and high-dose alkylator-based chemotherapy. J Clin Oncol. 2005;23:1491–9.
Teplick A, Kowalski M, Biegel JA, et al. Educational paper: screening in cancer predisposition syndromes: guidelines for the general pediatrician. Eur J Pediatr. 2011;170:285–94.
Tinat J, Bougeard G, Baert-Desurmont S, et al. 2009 version of the Chompret criteria for Li Fraumeni syndrome. J Clin Oncol. 2009; 27:e108–9; author reply e110.
Watanabe T, Vital A, Nobusawa S, et al. Selective acquisition of IDH1 R132C mutations in astrocytomas associated with Li-Fraumeni syndrome. Acta Neuropathol. 2009;117:653–6.
Zhukova N, Ramaswamy V, Remke M, et al. Subgroup-specific prognostic implications of TP53 mutation in medulloblastoma. J Clin Oncol. 2013;31:2927–35.
Villani A, Tabori U, Schiffman J, et al. Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: a prospective observational study. Lancet Oncol. 2011;12:559–67.
Kaelin Jr WG. The von Hippel-Lindau tumour suppressor protein: O2 sensing and cancer. Nat Rev Cancer. 2008;8:865–73.
Fisher PG, Tontiplaphol A, Pearlman EM, et al. Childhood cerebellar hemangioblastoma does not predict germline or somatic mutations in the von Hippel-Lindau tumor suppressor gene. Ann Neurol. 2002;51:257–60.
Lonser RR, Glenn GM, Walther M, et al. von Hippel-Lindau disease. Lancet. 2003;361:2059–67.
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Tabori, U., Laberge, AM., Ellezam, B., Carret, AS. (2015). Cancer Predisposition in Children with Brain Tumors. In: Scheinemann, K., Bouffet, E. (eds) Pediatric Neuro-oncology. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1541-5_8
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DOI: https://doi.org/10.1007/978-1-4939-1541-5_8
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