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Genetic Predisposition and Genetic Susceptibility

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Rare Tumors In Children and Adolescents

Part of the book series: Pediatric Oncology ((PEDIATRICO))

Abstract

More attention has been paid to the inherited nature of malignant tumors in children and adolescents, lately. Children with rare tumors may be at an increased risk of cancer because of a known cancer predisposition syndrome as Li-Fraumeni syndrome in case of adrenocortical tumors or multiple endocrine neoplasia (MEN2) in case of medullary thyroid tumors. Such cancer syndromes are commonly suspected in case of multiple malignancies within a family or a patient himself and/or in case of an adult-type tumor in children or adolescents. Interestingly though, it could be shown that strong predisposing mutations like BRCA1 and BRCA2, leading to individual risks of breast cancer of around 60% by age 70, together account for less than 5% of overall breast cancer incidence (Ponder 2001). Also, pediatric oncologists are not trained to pick up minor signs of cancer susceptibility, and therefore, syndromes might be overlooked. As discussed further down, it could be shown that the prevalence of minor and major morphological abnormalities is higher in patients with childhood cancers compared with controls – once more stressing the importance of constitutional genetic defects in pediatric oncogenesis and maybe pointing to so far unknown predisposition syndromes (Merks et al. 2008). This article gives an overview of mechanisms leading to cancer susceptibility, of known cancer syndromes (Table 6.1), and of the diagnostic approach and management, which can be followed in case of a suspected genetic predisposition for cancer.

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References

  • Agarwal SK, Lee BA, Sukhodolets KE, Kennedy PA, Obungu VH, Hickman AB, Mullendore ME, Whitten I, Skarulis MC, Simonds WF, Mateo C, Crabtree JS, Scacheri PC, Ji Y, Novotny EA, Garrett-Beal L, Ward JM, Libutti SK, Richard AH, Cerrato A, Parisi MJ, Santa A, Oliver B, Chandrasekharappa SC, Collins FS, Spiegel AM, Marx SJ (2004) Molecular pathology of the MEN1 gene. Ann N Y Acad Sci 1014:189–198

    PubMed  CAS  Google Scholar 

  • Allanson JE (1987) Noonan syndrome. J Med Genet 24(1):9–13

    PubMed  CAS  Google Scholar 

  • Antley RM, Hwang DS, Theopold W, Gorlin RJ, Steeper T, Pitt D, Danks DM, McPherson E, Bartels H, Wiedemann HR, Opitz JM (1981) Further delineation of the C (trigonocephaly) syndrome. Am J Med Genet 9(2):147–163

    PubMed  CAS  Google Scholar 

  • Aoki Y, Niihori T, Kawame H, Kurosawa K, Ohashi H, Tanaka Y, Filocamo M, Kato K, Suzuki Y, Kure S, Matsubara Y (2005) Germline mutations in HRAS proto-oncogene cause Costello syndrome. Nat Genet 37(10):1038–1040

    PubMed  CAS  Google Scholar 

  • Armour CM, Allanson JE (2008) Further delineation of cardio-facio-cutaneous syndrome: clinical features of 38 individuals with proven mutations. J Med Genet 45(4):249–254

    PubMed  CAS  Google Scholar 

  • Baskaran R, Wood LD, Whitaker LL, Canman CE, Morgan SE, Xu Y, Barlow C, Baltimore D, Wynshaw-Boris A, Kastan MB, Wang JY (1997) Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response to ionizing radiation. Nature 387(6632):516–519

    PubMed  CAS  Google Scholar 

  • Baty BJ, Blackburn BL, Carey JC (1994) Natural history of trisomy 18 and trisomy 13: I. Growth, physical assessment, medical histories, survival, and recurrence risk. Am J Med Genet 49(2):175–188

    PubMed  CAS  Google Scholar 

  • Baysal BE (2002) Hereditary paraganglioma targets diverse paraganglia. J Med Genet 39(9):617–622

    PubMed  CAS  Google Scholar 

  • Biesecker LG, Happle R, Mulliken JB, Weksberg R, Graham JM Jr, Viljoen DL, Cohen MM Jr (1999) Proteus syndrome: diagnostic criteria, differential diagnosis, and patient evaluation. Am J Med Genet 84(5):389–395

    PubMed  CAS  Google Scholar 

  • Binder G, Seidel AK, Weber K, Haase M, Wollmann HA, Ranke MB, Eggermann T (2006) IGF-II serum levels are normal in children with Silver-Russell syndrome who frequently carry epimutations at the IGF2 locus. J Clin Endocrinol Metab 91(11):4709–4712

    PubMed  CAS  Google Scholar 

  • Bliek J, Terhal P, van den Bogaard MJ, Maas S, Hamel B, Salieb-Beugelaar G, Simon M, Letteboer T, van der Smagt J, Kroes H, Mannens M (2006) Hypomethylation of the H19 gene causes not only Silver-Russell syndrome (SRS) but also isolated asymmetry or an SRS-like phenotype. Am J Hum Genet 78(4):604–614

    PubMed  CAS  Google Scholar 

  • Bliek J, Maas S, Alders M, Merks JH, Mannens M (2008) Epigenotype, phenotype, and tumors in patients with isolated hemihyperplasia. J Pediatr 153(1):95–100

    PubMed  CAS  Google Scholar 

  • Boder E (1975) Ataxia-telangiectasia: some historic, clinical and pathologic observations. Birth Defects Orig Artic Ser 11(1):255–270

    PubMed  CAS  Google Scholar 

  • Brandi ML, Gagel RF, Angeli A, Bilezikian JP, Beck-Peccoz P, Bordi C, Conte-Devolx B, Falchetti A, Gheri RG, Libroia A, Lips CJ, Lombardi G, Mannelli M, Pacini F, Ponder BA, Raue F, Skogseid B, Tamburrano G, Thakker RV, Thompson NW, Tomassetti P, Tonelli F, Wells SA Jr, Marx SJ (2001) Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 86(12):5658–5671

    PubMed  CAS  Google Scholar 

  • Brown S, Gersen S, Anyane-Yeboa K, Warburton D (1993) Preliminary definition of a “critical region” of chromosome 13 in q32: report of 14 cases with 13q deletions and review of the literature. Am J Med Genet 45(1):52–59

    PubMed  CAS  Google Scholar 

  • Caldwell PD, Smith DW (1972) The XXY (Klinefelter’s) syndrome in childhood: detection and treatment. J Pediatr 80(2):250–258

    PubMed  CAS  Google Scholar 

  • Carney JA (1995) Carney complex: the complex of myxomas, spotty pigmentation, endocrine overactivity, and schwannomas. Semin Dermatol 14(2):90–98

    PubMed  CAS  Google Scholar 

  • Carpten JD, Robbins CM, Villablanca A, Forsberg L, Presciuttini S, Bailey-Wilson J, Simonds WF, Gillanders EM, Kennedy AM, Chen JD, Agarwal SK, Sood R, Jones MP, Moses TY, Haven C, Petillo D, Leotlela PD, Harding B, Cameron D, Pannett AA, Hoog A, Heath H III, James-Newton LA, Robinson B, Zarbo RJ, Cavaco BM, Wassif W, Perrier ND, Rosen IB, Kristoffersson U, Turnpenny PD, Farnebo LO, Besser GM, Jackson CE, Morreau H, Trent JM, Thakker RV, Marx SJ, Teh BT, Larsson C, Hobbs MR (2002) HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nat Genet 32(4):676–680

    PubMed  CAS  Google Scholar 

  • Carter RF (2001) BRCA1, BRCA2 and breast cancer: a concise clinical review. Clin Invest Med 24(3):147–157

    PubMed  CAS  Google Scholar 

  • Cavallaro U, Christofori G (2004) Cell adhesion and signalling by cadherins and Ig-CAMs in cancer. Nat Rev Cancer 4(2):118–132

    PubMed  CAS  Google Scholar 

  • Choufani S, Shuman C, Weksberg R (2010) Beckwith-Wiedemann syndrome. Am J Med Genet C Semin Med Genet 154C(3):343–354

    PubMed  CAS  Google Scholar 

  • Cichowski K, Jacks T (2001) NF1 tumor suppressor gene function: narrowing the GAP. Cell 104(4):593–604

    PubMed  CAS  Google Scholar 

  • Clarren SK, Smith DW (1978) The fetal alcohol syndrome. N Engl J Med 298(19):1063–1067

    PubMed  CAS  Google Scholar 

  • Classon M, Harlow E (2002) The retinoblastoma tumour suppressor in development and cancer. Nat Rev Cancer 2(12):910–917

    PubMed  CAS  Google Scholar 

  • Cohen SB (1982) Familial polyposis coli and its extracolonic manifestations. J Med Genet 19(3):193–203

    PubMed  CAS  Google Scholar 

  • Cohen MM Jr (1989) A comprehensive and critical assessment of overgrowth and overgrowth syndromes. Adv Hum Genet 18:181–186

    PubMed  Google Scholar 

  • Cohen MM Jr, Howell RE (1999) Etiology of fibrous dysplasia and McCune-Albright syndrome. Int J Oral Maxillofac Surg 28(5):366–371

    PubMed  Google Scholar 

  • Cohen MM, Levy HP (1989) Chromosome instability syndromes. Adv Hum Genet 18:43–71

    PubMed  CAS  Google Scholar 

  • Cohen MM Jr, Gorlin RJ, Clark R, Ewing SG, Camfield PR (1993) Multiple circumferential skin folds and other anomalies: a problem in syndrome delineation. Clin Dysmorphol 2(1):39–46

    PubMed  Google Scholar 

  • Cole TR, Hughes HE (1994) Sotos syndrome: a study of the diagnostic criteria and natural history. J Med Genet 31(1):20–32

    PubMed  CAS  Google Scholar 

  • Curth HO, Hilberg AW, Machacek GF (1962) The site and histology of the cancer associated with malignant acanthosis nigricans. Cancer 15:364–382

    PubMed  CAS  Google Scholar 

  • Danon M, Crawford JD (1987) The McCune-Albright syndrome. Ergeb Inn Med Kinderheilkd 55:81–115

    PubMed  CAS  Google Scholar 

  • DeBaun MR, Ess J, Saunders S (2001) Simpson Golabi Behmel syndrome: progress toward understanding the molecular basis for overgrowth, malformation, and cancer predisposition. Mol Genet Metab 72(4):279–286

    PubMed  CAS  Google Scholar 

  • Douglas F, McHenry PM, Dagg JH, MacBeth FM, Morley WN (1994) Elevated levels of epidermal growth factor in a patient with tripe palms. Br J Dermatol 130(5):686–687

    PubMed  CAS  Google Scholar 

  • Dranoff G (2004) Cytokines in cancer pathogenesis and cancer therapy. Nat Rev Cancer 4(1):11–22

    PubMed  CAS  Google Scholar 

  • Ellis NA, German J (1996) Molecular genetics of Bloom’s syndrome. Hum Mol Genet 5 Spec No:1457–1463

    PubMed  CAS  Google Scholar 

  • Eng C, Clayton D, Schuffenecker I, Lenoir G, Cote G, Gagel RF, van Amstel HK, Lips CJ, Nishisho I, Takai SI, Marsh DJ, Robinson BG, Frank-Raue K, Raue F, Xue F, Noll WW, Romei C, Pacini F, Fink M, Niederle B, Zedenius J, Nordenskjold M, Komminoth P, Hendy GN, Mulligan LM (1996) The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis. JAMA 276(19):1575–1579

    PubMed  CAS  Google Scholar 

  • Engel JR, Smallwood A, Harper A, Higgins MJ, Oshimura M, Reik W, Schofield PN, Maher ER (2000) Epigenotype-phenotype correlations in Beckwith-Wiedemann syndrome. J Med Genet 37(12):921–926

    PubMed  CAS  Google Scholar 

  • Evans DG, Sainio M, Baser ME (2000) Neurofibromatosis type 2. J Med Genet 37(12):897–904

    PubMed  CAS  Google Scholar 

  • Fearnhead NS, Britton MP, Bodmer WF (2001) The ABC of APC. Hum Mol Genet 10(7):721–733

    PubMed  CAS  Google Scholar 

  • Felton KE, Gilchrist DM, Andrew SE (2007) Constitutive deficiency in DNA mismatch repair. Clin Genet 71(6):483–498

    PubMed  CAS  Google Scholar 

  • Fragale A, Tartaglia M, Wu J, Gelb BD (2004) Noonan syndrome-associated SHP2/PTPN11 mutants cause EGF-dependent prolonged GAB1 binding and sustained ERK2/MAPK1 activation. Hum Mutat 23(3):267–277

    PubMed  CAS  Google Scholar 

  • Friedberg EC (2001) How nucleotide excision repair protects against cancer. Nat Rev Cancer 1(1):22–33

    PubMed  CAS  Google Scholar 

  • German J (1993) Bloom syndrome: a mendelian prototype of somatic mutational disease. Medicine (Baltimore) 72(6):393–406

    CAS  Google Scholar 

  • Giampietro PF, Adler-Brecher B, Verlander PC, Pavlakis SG, Davis JG, Auerbach AD (1993) The need for more accurate and timely diagnosis in Fanconi anemia: a report from the International Fanconi Anemia Registry. Pediatrics 91(6):1116–1120

    PubMed  CAS  Google Scholar 

  • Goeteyn M, Geerts ML, Kint A, De Weert J (1994) The Bazex-Dupre-Christol syndrome. Arch Dermatol 130(3):337–342

    PubMed  CAS  Google Scholar 

  • Goldberg LH, Collins SA, Siegel DM (1987) The epidermal nevus syndrome: case report and review. Pediatr Dermatol 4(1):27–33

    PubMed  CAS  Google Scholar 

  • Gomez MR (ed) (1991) Tuberous Sclerosis and Allied Disorders: Clinical, Cellular, and Molecular Studies, vol 165. New York Academy of Science, New York

    Google Scholar 

  • Gorlin RJ (1987) Nevoid basal-cell carcinoma syndrome. Medicine (Baltimore) 66(2):98–113

    CAS  Google Scholar 

  • Gorlin RJ, Cohen MM Jr, Condon LM, Burke BA (1992) Bannayan-Riley-Ruvalcaba syndrome. Am J Med Genet 44(3):307–314

    PubMed  CAS  Google Scholar 

  • Goto M, Tanimoto K, Horiuchi Y, Sasazuki T (1981) Family analysis of Werner’s syndrome: a survey of 42 Japanese families with a review of the literature. Clin Genet 19(1):8–15

    PubMed  CAS  Google Scholar 

  • Greene MH (1997) Genetics of cutaneous melanoma and nevi. Mayo Clin Proc 72(5):467–474

    PubMed  CAS  Google Scholar 

  • Gutmann DH (2001) The neurofibromatoses: when less is more. Hum Mol Genet 10(7):747–755

    PubMed  CAS  Google Scholar 

  • Hall JG, Gilchrist DM (1990) Turner syndrome and its variants. Pediatr Clin North Am 37(6):1421–1440

    PubMed  CAS  Google Scholar 

  • Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70

    PubMed  CAS  Google Scholar 

  • Hanson JW (1986) Teratogen update: fetal hydantoin effects. Teratology 33(3):349–353

    PubMed  CAS  Google Scholar 

  • Hasle H, Clemmensen IH, Mikkelsen M (2000) Risks of leukaemia and solid tumours in individuals with Down’s syndrome. Lancet 355(9199):165–169

    PubMed  CAS  Google Scholar 

  • Hayflick L (1997) Mortality and immortality at the cellular level. A review. Biochemistry (Mosc) 62(11):1180–1190

    CAS  Google Scholar 

  • Hecht SS (2002) Cigarette smoking and lung cancer: chemical mechanisms and approaches to prevention. Lancet Oncol 3(8):461–469

    PubMed  CAS  Google Scholar 

  • Hemminki A, Peltomaki P, Mecklin JP, Jarvinen H, Salovaara R, Nystrom-Lahti M, de La CA, Aaltonen LA (1994) Loss of the wild type MLH1 gene is a feature of hereditary nonpolyposis colorectal cancer. Nat Genet 8(4):405–410

    PubMed  CAS  Google Scholar 

  • Hennekam RC (2003) Costello syndrome: an overview. Am J Med Genet 117C(1):42–48

    PubMed  Google Scholar 

  • Herbst AL, Kurman RJ, Scully RE (1972) Vaginal and cervical abnormalities after exposure to stilbestrol in utero. Obstet Gynecol 40(3):287–298

    PubMed  CAS  Google Scholar 

  • Hirschhorn R (2001) Glycogen storage disease type I. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular basis of inherited disease, 8th edn. McGraw-Hill, New York, pp 1530–1535

    Google Scholar 

  • Howe JR, Bair JL, Sayed MG, Anderson ME, Mitros FA, Petersen GM, Velculescu VE, Traverso G, Vogelstein B (2001) Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis. Nat Genet 28(2):184–187

    PubMed  CAS  Google Scholar 

  • Huret JL, Leonard C, Forestier B, Rethore MO, Lejeune J (1988) Eleven new cases of del(9p) and features from 80 cases. J Med Genet 25(11):741–749

    PubMed  CAS  Google Scholar 

  • Inoue H, Miki H, Oshimo K, Tanaka K, Monden Y, Yamamoto A, Kagawa S, Sano N, Hayashi E, Nagayama M (1995) Familial hyperparathyroidism associated with jaw fibroma: case report and literature review. Clin Endocrinol (Oxf) 43(2):225–229

    CAS  Google Scholar 

  • Itoh H, Hirata K, Ohsato K (1993) Turcot’s syndrome and familial adenomatous polyposis associated with brain tumor: review of related literature. Int J Colorectal Dis 8(2):87–94

    PubMed  CAS  Google Scholar 

  • Jones KL (2006) Smith’s Recognizable patterns of human malformation, 6th edn. Elsevier Saunders, Philadelphia

    Google Scholar 

  • Jorquera R, Tanguay RM (2001) Fumarylacetoacetate, the metabolite accumulating in hereditary tyrosinemia, activates the ERK pathway and induces mitotic abnormalities and genomic instability. Hum Mol Genet 10(17):1741–1752

    PubMed  CAS  Google Scholar 

  • Kaelin WG Jr (2002) Molecular basis of the VHL hereditary cancer syndrome. Nat Rev Cancer 2(9):673–682

    PubMed  CAS  Google Scholar 

  • Kallijarvi J, Avela K, Lipsanen-Nyman M, Ulmanen I, Lehesjoki AE (2002) The TRIM37 gene encodes a peroxisomal RING-B-box-coiled-coil protein: classification of mulibrey nanism as a new peroxisomal disorder. Am J Hum Genet 70(5):1215–1228

    PubMed  CAS  Google Scholar 

  • Karlberg N, Jalanko H, Perheentupa J, Lipsanen-Nyman M (2004) Mulibrey nanism: clinical features and diagnostic criteria. J Med Genet 41(2):92–98

    PubMed  CAS  Google Scholar 

  • Kiess W, Linderkamp O, Hadorn HB, Haas R (1984) Fetal alcohol syndrome and malignant disease. Eur J Pediatr 143(2):160–161

    PubMed  CAS  Google Scholar 

  • Kitao S, Shimamoto A, Goto M, Miller RW, Smithson WA, Lindor NM, Furuichi Y (1999) Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome. Nat Genet 22(1):82–84

    PubMed  CAS  Google Scholar 

  • Klamt B, Koziell A, Poulat F, Wieacker P, Scambler P, Berta P, Gessler M (1998) Frasier syndrome is caused by defective alternative splicing of WT1 leading to an altered ratio of WT1 +/−KTS splice isoforms. Hum Mol Genet 7(4):709–714

    PubMed  CAS  Google Scholar 

  • Knudson AG Jr, Hethcote HW, Brown BW (1975) Mutation and childhood cancer: a probabilistic model for the incidence of retinoblastoma. Proc Natl Acad Sci USA 72(12):5116–5120

    PubMed  Google Scholar 

  • Korsmeyer SJ (1992) Chromosomal translocations in lymphoid malignancies reveal novel proto-oncogenes. Annu Rev Immunol 10:785–807

    PubMed  CAS  Google Scholar 

  • Kvittingen EA (1991) Tyrosinaemia type I–an update. J Inherit Metab Dis 14(4):554–562

    PubMed  CAS  Google Scholar 

  • Kwiatkowski DJ (2003) Rhebbing up mTOR: new insights on TSC1 and TSC2, and the pathogenesis of tuberous sclerosis. Cancer Biol Ther 2(5):471–476

    PubMed  CAS  Google Scholar 

  • Landy SJ, Donnai D (1993) Incontinentia pigmenti (Bloch-Sulzberger syndrome). J Med Genet 30(1):53–59

    PubMed  CAS  Google Scholar 

  • Levine AJ (1997) p53, the cellular gatekeeper for growth and division. Cell 88(3):323–331

    PubMed  CAS  Google Scholar 

  • Lewis RJ, Ketcham AS (1973) Maffucci’s syndrome: functional and neoplastic significance. Case report and review of the literature. J Bone Joint Surg Am 55(7):1465–1479

    PubMed  CAS  Google Scholar 

  • Li FP, Fraumeni JF Jr, Mulvihill JJ, Blattner WA, Dreyfus MG, Tucker MA, Miller RW (1988) A cancer family syndrome in twenty-four kindreds. Cancer Res 48(18):5358–5362

    PubMed  CAS  Google Scholar 

  • Limmer J, Fleig WE, Leupold D, Bittner R, Ditschuneit H, Beger HG (1988) Hepatocellular carcinoma in type I glycogen storage disease. Hepatology 8(3):531–537

    PubMed  CAS  Google Scholar 

  • Lindhurst MJ, et al. (2011) A mosaic activating mutation in AKT1 associated with the proteus syndrome. N Engl J Med 365(7):611–619

    PubMed  CAS  Google Scholar 

  • Little M, Wells C (1997) A clinical overview of WT1 gene mutations. Hum Mutat 9(3):209–225

    PubMed  CAS  Google Scholar 

  • Lonser RR, Glenn GM, Walther M, Chew EY, Libutti SK, Linehan WM, Oldfield EH (2003) von Hippel-Lindau disease. Lancet 361(9374):2059–2067

    PubMed  CAS  Google Scholar 

  • Lukas J, Parry D, Aagaard L, Mann DJ, Bartkova J, Strauss M, Peters G, Bartek J (1995) Retinoblastoma-protein-dependent cell-cycle inhibition by the tumour suppressor p16. Nature 375(6531):503–506

    PubMed  CAS  Google Scholar 

  • Lynch HT, de La CA (1999) Genetic susceptibility to non-polyposis colorectal cancer. J Med Genet 36(11):801–818

    PubMed  CAS  Google Scholar 

  • Maher ER, Eng C (2002) The pressure rises: update on the genetics of phaeochromocytoma. Hum Mol Genet 11(20):2347–2354

    PubMed  CAS  Google Scholar 

  • Makitie O, Sulisalo T, de la Chapelle A, Kaitila I (1995) Cartilage-hair hypoplasia. J Med Genet 32(1):39–43

    PubMed  CAS  Google Scholar 

  • Mathew CG (2006) Fanconi anaemia genes and susceptibility to cancer. Oncogene 25(43):5875–5884

    PubMed  CAS  Google Scholar 

  • Merks JH, Caron HN, Hennekam RC (2005) High incidence of malformation syndromes in a series of 1,073 children with cancer. Am J Med Genet A 134(2):132–143

    Google Scholar 

  • Merks JH, Ozgen HM, Koster J, Zwinderman AH, Caron HN, Hennekam RC (2008) Prevalence and patterns of morphological abnormalities in patients with childhood cancer. JAMA 299(1):61–69

    PubMed  CAS  Google Scholar 

  • Meyers GA, Orlow SJ, Munro IR, Przylepa KA, Jabs EW (1995) Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans. Nat Genet 11(4):462–464

    PubMed  CAS  Google Scholar 

  • Mohaghegh P, Hickson ID (2001) DNA helicase deficiencies associated with cancer predisposition and premature ageing disorders. Hum Mol Genet 10(7):741–746

    PubMed  CAS  Google Scholar 

  • Montanaro L, Brigotti M, Clohessy J, Barbieri S, Ceccarelli C, Santini D, Taffurelli M, Calienni M, Teruya-Feldstein J, Trere D, Pandolfi PP, Derenzini M (2006) Dyskerin expression influences the level of ribosomal RNA pseudo-uridylation and telomerase RNA component in human breast cancer. J Pathol 210(1):10–18

    PubMed  CAS  Google Scholar 

  • Montminy M (1997) Transcriptional regulation by cyclic AMP. Annu Rev Biochem 66:807–822

    PubMed  CAS  Google Scholar 

  • Moorthy AV, Chesney RW, Lubinsky M (1987) Chronic renal failure and XY gonadal dysgenesis: “Frasier” syndrome–a commentary on reported cases. Am J Med Genet Suppl 3:297–302

    PubMed  CAS  Google Scholar 

  • Morrison PJ, Nevin NC (1996) Multiple endocrine neoplasia type 2B (mucosal neuroma syndrome, Wagenmann-Froboese syndrome). J Med Genet 33(9):779–782

    PubMed  CAS  Google Scholar 

  • Mueller RF (1994) The Denys-Drash syndrome. J Med Genet 31(6):471–477

    PubMed  CAS  Google Scholar 

  • Nadeau JH (2001) Modifier genes in mice and humans. Nat Rev Genet 2(3):165–174

    PubMed  CAS  Google Scholar 

  • Neri G, Gurrieri F, Zanni G, Lin A (1998) Clinical and molecular aspects of the Simpson-Golabi-Behmel syndrome. Am J Med Genet 79(4):279–283

    PubMed  CAS  Google Scholar 

  • Nicolaides NC, Papadopoulos N, Liu B, Wei YF, Carter KC, Ruben SM, Rosen CA, Haseltine WA, Fleischmann RD, Fraser CM (1994) Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. Nature 371(6492):75–80

    PubMed  CAS  Google Scholar 

  • Niihori T, Aoki Y, Narumi Y, Neri G, Cave H, Verloes A, Okamoto N, Hennekam RC, Gillessen-Kaesbach G, Wieczorek D, Kavamura MI, Kurosawa K, Ohashi H, Wilson L, Heron D, Bonneau D, Corona G, Kaname T, Naritomi K, Baumann C, Matsumoto N, Kato K, Kure S, Matsubara Y (2006) Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome. Nat Genet 38(3):294–296

    PubMed  CAS  Google Scholar 

  • Patton MA (1988) Russell-Silver syndrome. J Med Genet 25(8):557–560

    PubMed  CAS  Google Scholar 

  • Patton MA, Sharma A, Winter RM (1985) The Aase-Smith syndrome. Clin Genet 28(6):521–525

    PubMed  CAS  Google Scholar 

  • Paull TT, Gellert M (1999) Nbs1 potentiates ATP-driven DNA unwinding and endonuclease cleavage by the Mre11/Rad50 complex. Genes Dev 13(10):1276–1288

    PubMed  CAS  Google Scholar 

  • Peto J (2001) Cancer epidemiology in the last century and the next decade. Nature 411(6835):390–395

    PubMed  CAS  Google Scholar 

  • Petrij F, Giles RH, Dauwerse HG, Saris JJ, Hennekam RC, Masuno M, Tommerup N, van Ommen GJ, Goodman RH, Peters DJ (1995) Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP. Nature 376(6538):348–351

    PubMed  CAS  Google Scholar 

  • Pilarski R, Eng C (2004) Will the real Cowden syndrome please stand up (again)? Expanding mutational and clinical spectra of the PTEN hamartoma tumour syndrome. J Med Genet 41(5):323–326

    PubMed  CAS  Google Scholar 

  • Ponder BA (2001) Cancer genetics. Nature 411(6835):336–341

    PubMed  CAS  Google Scholar 

  • Pueschel SM (1990) Clinical aspects of Down syndrome from infancy to adulthood. Am J Med Genet Suppl 7:52–56

    PubMed  CAS  Google Scholar 

  • Rahman N, Scott RH (2007) Cancer genes associated with phenotypes in monoallelic and biallelic mutation carriers: new lessons from old players. Hum Mol Genet 16 Spec No 1:R60–R66

    PubMed  Google Scholar 

  • Rauscher FJ III (1993) The WT1 Wilms tumor gene product: a developmentally regulated transcription factor in the kidney that functions as a tumor suppressor. FASEB J 7(10):896–903

    PubMed  CAS  Google Scholar 

  • Riccardi VM (1977) Trisomy 8: an international study of 70 patients. Birth Defects Orig Artic Ser 13(3C):171–184

    PubMed  CAS  Google Scholar 

  • Riccardi VM, Sujansky E, Smith AC, Francke U (1978) Chromosomal imbalance in the Aniridia-Wilms’ tumor association: 11p interstitial deletion. Pediatrics 61(4):604–610

    PubMed  CAS  Google Scholar 

  • Ridanpaa M, van Eenennaam H, Pelin K, Chadwick R, Johnson C, Yuan B, van Venrooij W, Pruijn G, Salmela R, Rockas S, Makitie O, Kaitila I, de la CA (2001) Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia. Cell 104(2):195–203

    PubMed  CAS  Google Scholar 

  • Rubinstein JH (1990) Broad thumb-hallux (Rubinstein-Taybi) syndrome 1957–1988. Am J Med Genet Suppl 6:3–16

    PubMed  CAS  Google Scholar 

  • Ruhrberg C, Williamson JA, Sheer D, Watt FM (1996) Chromosomal localisation of the human envoplakin gene (EVPL) to the region of the tylosis oesophageal cancer gene (TOCG) on 17q25. Genomics 37(3):381–385

    PubMed  CAS  Google Scholar 

  • Schmidt L, Duh FM, Chen F, Kishida T, Glenn G, Choyke P, Scherer SW, Zhuang Z, Lubensky I, Dean M, Allikmets R, Chidambaram A, Bergerheim UR, Feltis JT, Casadevall C, Zamarron A, Bernues M, Richard S, Lips CJ, Walther MM, Tsui LC, Geil L, Orcutt ML, Stackhouse T, Zbar B (1997) Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat Genet 16(1):68–73

    PubMed  CAS  Google Scholar 

  • Schuman SH, Burton WE (1979) A new osteosarcoma/­malformation syndrome. Clin Genet 15(5):462–463

    PubMed  CAS  Google Scholar 

  • Scully R (2000) Role of BRCA gene dysfunction in breast and ovarian cancer predisposition. Breast Cancer Res 2(5):324–330

    PubMed  CAS  Google Scholar 

  • Sijmons RH (ed) Familial Cancer Database. http://www.facd.info.

  • Sirinavin C, Trowbridge AA (1975) Dyskeratosis congenita: clinical features and genetic aspects. Report of a family and review of the literature. J Med Genet 12(4):339–354

    PubMed  CAS  Google Scholar 

  • Smahi A, Courtois G, Vabres P, Yamaoka S, Heuertz S, Munnich A, Israel A, Heiss NS, Klauck SM, Kioschis P, Wiemann S, Poustka A, Esposito T, Bardaro T, Gianfrancesco F, Ciccodicola A, D’Urso M, Woffendin H, Jakins T, Donnai D, Stewart H, Kenwrick SJ, Aradhya S, Yamagata T, Levy M, Lewis RA, Nelson DL (2000) Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) Consortium. Nature 405(6785):466–472

    PubMed  CAS  Google Scholar 

  • Takahashi M (2001) The GDNF/RET signaling pathway and human diseases. Cytokine Growth Factor Rev 12(4):361–373

    PubMed  CAS  Google Scholar 

  • Teitz T, Wei T, Valentine MB, Vanin EF, Grenet J, Valentine VA, Behm FG, Look AT, Lahti JM, Kidd VJ (2000) Caspase 8 is deleted or silenced preferentially in childhood neuroblastomas with amplification of MYCN. Nat Med 6(5):529–535

    PubMed  CAS  Google Scholar 

  • Thakker RV (1998) Multiple endocrine neoplasia–syndromes of the twentieth century. J Clin Endocrinol Metab 83(8):2617–2620

    PubMed  CAS  Google Scholar 

  • Tlsty TD, Hein PW (2001) Know thy neighbor: stromal cells can contribute oncogenic signals. Curr Opin Genet Dev 11(1):54–59

    PubMed  CAS  Google Scholar 

  • Tomlinson IP, Alam NA, Rowan AJ, Barclay E, Jaeger EE, Kelsell D, Leigh I, Gorman P, Lamlum H, Rahman S, Roylance RR, Olpin S, Bevan S, Barker K, Hearle N, Houlston RS, Kiuru M, Lehtonen R, Karhu A, Vilkki S, Laiho P, Eklund C, Vierimaa O, Aittomaki K, Hietala M, Sistonen P, Paetau A, Salovaara R, Herva R, Launonen V, Aaltonen LA (2002) Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat Genet 30(4):406–410

    PubMed  CAS  Google Scholar 

  • Tsukahara M, Opitz JM (1996) Dubowitz syndrome: review of 141 cases including 36 previously unreported patients. Am J Med Genet 63(1):277–289

    PubMed  CAS  Google Scholar 

  • Tyldesley WR, Hughes RO (1973) Letter: Tylosis, leukoplakia, and oesophageal carcinoma. Br Med J 4(5889):427

    PubMed  CAS  Google Scholar 

  • van der Burgt I, Chrzanowska KH, Smeets D, Weemaes C (1996) Nijmegen breakage syndrome. J Med Genet 33(2):153–156

    PubMed  Google Scholar 

  • Varon R, Vissinga C, Platzer M, Cerosaletti KM, Chrzanowska KH, Saar K, Beckmann G, Seemanova E, Cooper PR, Nowak NJ, Stumm M, Weemaes CM, Gatti RA, Wilson RK, Digweed M, Rosenthal A, Sperling K, Concannon P, Reis A (1998) Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell 93(3):467–476

    PubMed  CAS  Google Scholar 

  • Vasen HF, Watson P, Mecklin JP, Lynch HT (1999) New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology 116(6):1453–1456

    PubMed  CAS  Google Scholar 

  • Veale AM, McColl I, Bussey HJ, Morson BC (1966) Juvenile polyposis coli. J Med Genet 3(1):5–16

    PubMed  CAS  Google Scholar 

  • Villavicencio EH, Walterhouse DO, Iannaccone PM (2000) The sonic hedgehog-patched-gli pathway in human development and disease. Am J Hum Genet 67(5):1047–1054

    PubMed  CAS  Google Scholar 

  • Viskochil D (1999) Neurofibromatosis 1. Am J Med Genet 89(1):V–VIII

    CAS  Google Scholar 

  • Waite KA, Eng C (2002) Protean PTEN: form and function. Am J Hum Genet 70(4):829–844

    PubMed  CAS  Google Scholar 

  • Wang LL, Levy ML, Lewis RA, Chintagumpala MM, Lev D, Rogers M, Plon SE (2001a) Clinical manifestations in a cohort of 41 Rothmund-Thomson syndrome patients. Am J Med Genet 102(1):11–17

    PubMed  CAS  Google Scholar 

  • Wang X, Yeh S, Wu G, Hsu CL, Wang L, Chiang T, Yang Y, Guo Y, Chang C (2001b) Identification and characterization of a novel androgen receptor coregulator ARA267-alpha in prostate cancer cells. J Biol Chem 276(44):40417–40423

    PubMed  CAS  Google Scholar 

  • Wawersik S, Maas RL (2000) Vertebrate eye development as modeled in Drosophila. Hum Mol Genet 9(6):917–925

    PubMed  CAS  Google Scholar 

  • Weinberg RA (1995) The retinoblastoma protein and cell cycle control. Cell 81(3):323–330

    PubMed  CAS  Google Scholar 

  • Weinstein LS, Shenker A, Gejman PV, Merino MJ, Friedman E, Spiegel AM (1991) Activating mutations of the stimulatory G protein in the McCune-Albright syndrome. N Engl J Med 325(24):1688–1695

    PubMed  CAS  Google Scholar 

  • Westerman AM, Entius MM, de Baar E, Boor PP, Koole R, van Velthuysen ML, Offerhaus GJ, Lindhout D, de Rooij FW, Wilson JH (1999) Peutz-Jeghers syndrome: 78-year follow-up of the original family. Lancet 353(9160):1211–1215

    PubMed  CAS  Google Scholar 

  • Winter RM, Baraitser M (2009) The Winter-Baraitser Dysmorphology Database (WBDD). London Medical Data­bases ltd, London

    Google Scholar 

  • Wyllie JP, Wright MJ, Burn J, Hunter S (1994) Natural history of trisomy 13. Arch Dis Child 71(4):343–345

    PubMed  CAS  Google Scholar 

  • Yoo LI, Chung DC, Yuan J (2002) LKB1–a master tumour suppressor of the small intestine and beyond. Nat Rev Cancer 2(7):529–535

    PubMed  CAS  Google Scholar 

  • Zbar B, Glenn G, Lubensky I, Choyke P, Walther MM, Magnusson G, Bergerheim US, Pettersson S, Amin M, Hurley K (1995) Hereditary papillary renal cell carcinoma: clinical studies in 10 families. J Urol 153(3 Pt 2):907–912

    PubMed  CAS  Google Scholar 

  • Zhang Y, Musci T, Derynck R (1997) The tumor suppressor Smad4/DPC 4 as a central mediator of Smad function. Curr Biol 7(4):270–276

    PubMed  Google Scholar 

  • Zhou XP, Hampel H, Thiele H, Gorlin RJ, Hennekam RC, Parisi M, Winter RM, Eng C (2001) Association of germline mutation in the PTEN tumour suppressor gene and Proteus and Proteus-like syndromes. Lancet 358(9277):210–211

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Pediatric Oncologist, Emma Children’s Hospital – Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Johannes H. M. Merks

  2. Department of Pediatric Hematology/Oncology, University Children’s Hospital Erlangen, Loschgestrasse 15, 91054, Erlangen, Germany

    Ines B. Brecht

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  1. Johannes H. M. Merks
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  2. Ines B. Brecht
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Correspondence to Johannes H. M. Merks .

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Editors and Affiliations

  1. Klinik für Kinder- und Jugendmedizin, Klinikum Dortmund gGmbH, Beurhausstr. 40, Dortmund, 44137, Germany

    Dominik T. Schneider

  2. Klinik für Kinder und Jugendliche, Universitätsklinikum Erlangen-Nürnberg, Loschgestr. 15, Erlangen, 91054, Germany

    Ines B. Brecht

  3. at Egleston, Dept. Pediatric Hematology/Oncology, Children's Healthcare of Atlanta, Uppergate Drive NE., 2015, Atlanta, 30322, Georgia, USA

    Thomas A. Olson

  4. Unità di Oncologia Pediatrica, Istituto Nazionale Tumori, Via G. Venezian 1, Milano, 20133, Italy

    Andrea Ferrari

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Merks, J.H.M., Brecht, I.B. (2012). Genetic Predisposition and Genetic Susceptibility. In: Schneider, D., Brecht, I., Olson, T., Ferrari, A. (eds) Rare Tumors In Children and Adolescents. Pediatric Oncology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-04197-6_6

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