Skip to main content
SpringerLink
Log in
Book cover

The Surgery of Childhood Tumors pp 35–50Cite as

Screening for Genetic Susceptibility to Paediatric Tumours

  • Chapter
  • First Online:

Abstract

About 5 % of all malignant tumours arise in individuals who have an underlying genetic predisposition due to a single high risk gene. The proportion in children is probably higher but is currently unknown but is estimated as 10–20 % or more, and a much larger proportion may be in part due to lower risk susceptibility genes.

Children and adolescents with a tumour susceptibility may only be recognised to have an underlying predisposition when they present with a tumour but sometimes may be identified as at risk through their family history or because they have an identifiable phenotype, known to be associated with an increased chance of developing a tumour. If this is the case presymptomatic clinical and/or genetic screening may be appropriate. This should only be done within the context of adequate genetic counselling.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Astuti D, Morris MR, Cooper WN, Staals RHJ, Wake NC, Fews GA, Gill H, et al. Germline mutations in DIS3L2 cause the Perlman syndrome of overgrowth and Wilms tumor susceptibility. Nat Genet. 2012;44(3):277–84. doi:10.1038/ng.1071.

    Article  CAS  PubMed  Google Scholar 

  2. Beggs AD, Latchford A, Vasen HFA, Moslein G, Alonso A, Aretz S, Bertario L, et al. Peutz-Jeghers syndrome: a systematic review and recommendations for management. Gut. 2010. doi:10.1136/gut.2009.198499.

    PubMed  Google Scholar 

  3. Birch JM, Alston RD, McNally RJ, Evans DG, Kelsey AM, Harris M, Eden OB, et al. Relative frequency and morphology of cancers in carriers of germline TP53 mutations. Oncogene. 2001;20(34):4621–8. doi:10.1038/sj.onc.1204621.

    Article  CAS  PubMed  Google Scholar 

  4. Blakeley JO, Evans DG, Adler J, Brackmann D, Ferner RE, Hanemann CO, Harris G, et al. Consensus recommendations. Consensus. 2013;(1):24–41. doi:10.1002/ajmg.a.34359.

    Google Scholar 

  5. Blumenthal GM, Dennis PA. PTEN hamartoma tumor syndromes. Eur J Hum Genet EJHG. 2008;16(11):1289–300. doi:10.1038/ejhg.2008.162.

    Article  CAS  PubMed  Google Scholar 

  6. Bourdeaut F, Lequin D, Brugières L, Reynaud S, Dufour C, Doz F, André N, et al. Frequent hSNF5/INI1 germline mutations in patients with rhabdoid tumor. Clin Cancer Res Off J Am Assoc Cancer Res. 2011;17(1):31–8. doi:10.1158/1078-0432.CCR-10-1795.

    Article  CAS  Google Scholar 

  7. Brandi ML, Gagel RF, Angeli A, Bilezikian JP, Beck-Peccoz P, Bordi C, Conte-Devolx B, et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. 2001;86(12):5658–71.

    Article  CAS  PubMed  Google Scholar 

  8. Brouwers FM, Eisenhofer G, Tao JJ, Kant JA, Adams KT, Linehan WM, Pacak K. High frequency of SDHB germline mutations in patients with malignant catecholamine-producing paragangliomas: implications for genetic testing. J Clin Endocrinol Metab. 2006;91(11):4505–9.

    Article  CAS  PubMed  Google Scholar 

  9. Brugières L, Pierron G, Chompret A, Paillerets BB, Di Rocco F, Varlet P, Pierre-Kahn A, et al. Incomplete penetrance of the predisposition to medulloblastoma associated with germ-line SUFU mutations. J Med Genet. 2010;47(2):142–4.

    Article  PubMed  Google Scholar 

  10. Brugières L, Remenieras A, Pierron G, Varlet P, Forget S, Byrde V, Bombled J, et al. High frequency of germline SUFU mutations in children with desmoplastic/nodular medulloblastoma younger than 3 years of age. J Clin Oncol Off J Am Soc Clin Oncol. 2012;30(17):2087–93.

    Article  Google Scholar 

  11. Choong SS, Latiff ZA, Mohamed M, Lim LLW, Chen KS, Vengidasan L, Razali H, et al. Childhood adrenocortical carcinoma as a sentinel cancer for detecting families with germline TP53 mutations. Clin Genet. 2012;82(6):564–8.

    Article  CAS  PubMed  Google Scholar 

  12. Decker RA, Peacock ML, Watson P. Hirschsprung disease in MEN 2A: increased spectrum of RET exon 10 genotypes and strong genotype-phenotype correlation. Hum Mol Genet. 1998;7(1):129–34.

    Article  CAS  PubMed  Google Scholar 

  13. Dempsey-Robertson M, Wilkes D, Stall A, Bush P. Incidence of abdominal tumors in syndromic and idiopathic hemihypertrophy/isolated hemihyperplasia. J Pediatr Orthop. 2012;32(3):322–6.

    Article  PubMed  Google Scholar 

  14. Desai DC, Murday V, Phillips RK, Neale KF, Milla P, Hodgson SV. A survey of phenotypic features in juvenile polyposis. J Med Genet. 1998;35(6):476–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Doppman JL, Travis WD, Nieman L, Miller DL, Chrousos GP, Gomez MT, Cutler GB, et al. Cushing syndrome due to primary pigmented nodular adrenocortical disease: findings at CT and MR imaging. Radiology. 1989;172(2):415–20.

    Article  CAS  PubMed  Google Scholar 

  16. Dumić M, Ille J, Batinica S, Cacić M, Cvitanović M, Marinović B, Plavsić V, et al. Primary adrenocortical micronodular dysplasia. Lijec Vjesn. 1999;121(1–2):22–6.

    PubMed  Google Scholar 

  17. Durno CA, Aronson M, Tabori U, Malkin D, Gallinger S, Chan HSL. Oncologic surveillance for subjects with biallelic mismatch repair gene mutations: 10 year follow-up of a kindred. Pediatr Blood Cancer. 2012;59(4):652–6.

    Article  PubMed  Google Scholar 

  18. Durno CA, Gallinger S. Genetic predisposition to colorectal cancer: new pieces in the pediatric puzzle. J Pediatr Gastroenterol Nutr. 2006;43(1):5–15.

    Article  PubMed  Google Scholar 

  19. Elitsur Y, Teitelbaum JE, Rewalt M, Nowicki M. Clinical and endoscopic data in juvenile polyposis syndrome in preadolescent children: a multicenter experience from the United States. J Clin Gastroenterol. 2009;43(8):734–6.

    Article  PubMed  Google Scholar 

  20. Erlic Z, Neumann HPH. When should genetic testing be obtained in a patient with phaeochromocytoma or paraganglioma? Clin Endocrinol (Oxf). 2009;70(3):354–7.

    Article  Google Scholar 

  21. Evans DGR, Huson SM, Birch JM. Malignant peripheral nerve sheath tumours in inherited disease. Clin Sarcoma Res. 2012;2(1):17. doi:10.1186/2045-3329-2-17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Fenton PA, Clarke SE, Owen W, Hibbert J, Hodgson SV. Cribriform variant papillary thyroid cancer: a characteristic of familial adenomatous polyposis. Thyroid Off J Am Thyroid Assoc. 2001;11(2):193–7.

    Article  CAS  Google Scholar 

  23. Ferner RE, Huson SM, Thomas N, Moss C, Willshaw H, Evans DG, Upadhyaya M, et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet. 2007;44(2):81–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Gadelha MR, Trivellin G, Hernández Ramírez LC, Korbonits M. Genetics of pituitary adenomas. Front Horm Res. 2013;41:111–40.

    Article  CAS  PubMed  Google Scholar 

  25. Georgitsi M, De Menis E, Cannavò S, Mäkinen MJ, Tuppurainen K, Pauletto P, Curtò L, et al. Aryl hydrocarbon receptor interacting protein (AIP) gene mutation analysis in children and adolescents with sporadic pituitary adenomas. Clin Endocrinol (Oxf). 2008;69(4):621–7.

    Article  CAS  Google Scholar 

  26. Gourgari E, Saloustros E, Stratakis CA. Large-cell calcifying Sertoli cell tumors of the testes in pediatrics. Curr Opin Pediatr. 2012;24(4):518–22.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Gracia Bouthelier R, Lapunzina P. Follow-up and risk of tumors in overgrowth syndromes. J Pediatr Endocrinol Metab JPEM. 2005;18 Suppl 1:1227–35.

    PubMed  Google Scholar 

  28. Gripp KW. Tumor predisposition in Costello syndrome. Am J Med Genet C Semin Med Genet. 2005;137C(1):72–7.

    Article  PubMed  Google Scholar 

  29. Guaragna MS, Lutaif AC, Bittencourt VB, Piveta CS, Soardi FC, Castro LC, Belangero VMS, et al. Frasier syndrome: four new cases with unusual presentations. Arq Bras Endocrinol Metabol. 2012;56(8):525–32.

    Article  PubMed  Google Scholar 

  30. Hanks S, Coleman K, Reid S, Plaja A, Firth H, Fitzpatrick D, Kidd A, et al. Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B. Nat Genet. 2004;36(11):1159–61.

    Article  CAS  PubMed  Google Scholar 

  31. Harris R, Lane B, Harris H, Williamson P, Dodge J, Modell B, Ponder B, et al. National Confidential Enquiry into counselling for genetic disorders by non-geneticists: general recommendations and specific standards for improving care. Br J Obstet Gynaecol. 1999;106(7):658–63.

    Article  CAS  PubMed  Google Scholar 

  32. Hennekam RCM. Costello syndrome: an overview. Am J Med Genet C Semin Med Genet. 2003;117C(1):42–8.

    Article  PubMed  Google Scholar 

  33. Herkert JC, Niessen RC, Olderode-Berends MJW, Veenstra-Knol HE, Vos YJ, Van der Klift HM, Scheenstra R, et al. Paediatric intestinal cancer and polyposis due to bi-allelic PMS2 mutations: case series, review and follow-up guidelines. Eur J Cancer. 2011;47(7):965–82.

    Article  CAS  PubMed  Google Scholar 

  34. Huson SM, Harper PS, Compston DA. Von Recklinghausen neurofibromatosis. A clinical and population study in south-east Wales. Brain J Neurol. 1988;111(Pt 6):1355–81.

    Article  Google Scholar 

  35. Kirschner LS, Sandrini F, Monbo J, Lin JP, Carney JA, Stratakis CA. Genetic heterogeneity and spectrum of mutations of the PRKAR1A gene in patients with the carney complex. Hum Mol Genet. 2000;9(20):3037–46.

    Article  CAS  PubMed  Google Scholar 

  36. Kratz CP, Rapisuwon S, Reed H, Hasle H, Rosenberg PS. Cancer in Noonan, Costello, cardiofaciocutaneous and LEOPARD syndromes. Am J Med Genet C Semin Med Genet. 2011;157(2):83–9.

    Article  PubMed Central  Google Scholar 

  37. Krüger S, Kinzel M, Walldorf C, Gottschling S, Bier A, Tinschert S, Von Stackelberg A, et al. Homozygous PMS2 germline mutations in two families with early-onset haematological malignancy, brain tumours, HNPCC-associated tumours, and signs of neurofibromatosis type 1. Eur J Hum Genet. 2008;16(1):62–72.

    Article  PubMed  Google Scholar 

  38. Kulkarni A, Iii DMW. The involvement of DNA-damage and -repair defects in neurological dysfunction, (march), 539–566. 2008.

    Google Scholar 

  39. Langer P, Cupisti K, Bartsch DK, Nies C, Goretzki PE, Rothmund M, Röher HD. Adrenal involvement in multiple endocrine neoplasia type 1. World J Surg. 2002;26(8):891–6.

    Article  PubMed  Google Scholar 

  40. Maher ER, Reik W. Beckwith-Wiedemann syndrome: imprinting in clusters revisited. J Clin Invest. 2000;105(3):247–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Malkin D. Li-fraumeni syndrome. Genes Cancer. 2011;2(4):475–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. McIntyre JF, Smith-Sorensen B, Friend SH, Kassell J, Borresen AL, Yan YX, Russo C, et al. Germline mutations of the p53 tumor suppressor gene in children with osteosarcoma. J Clin Oncol. 1994;12(5):925–30.

    CAS  PubMed  Google Scholar 

  43. Mossé YP, Laudenslager M, Longo L, Cole KA, Wood A, Attiyeh EF, Laquaglia MJ, et al. Identification of ALK as a major familial neuroblastoma predisposition gene. Nature. 2008;455(7215):930–5.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Neumann HPH, Bausch B, McWhinney SR, Bender BU, Gimm O, Franke G, Schipper J, et al. Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med. 2002;346(19):1459–66.

    Article  CAS  PubMed  Google Scholar 

  45. Ng D, Stavrou T, Liu L, Taylor MD, Gold B, Dean M, Kelley MJ, et al. Retrospective family study of childhood medulloblastoma. Am J Med Genet A. 2005;134(4):399–403.

    Article  PubMed  Google Scholar 

  46. Nozières C, Berlier P, Dupuis C, Raynaud-Ravni C, Morel Y, Chazot FB, Nicolino M. Sporadic and genetic forms of paediatric somatotropinoma: a retrospective analysis of seven cases and a review of the literature. Orphanet J Rare Dis. 2011;6:67.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Oostra AB, Nieuwint AWM, Joenje H, De Winter JP. Diagnosis of fanconi anemia: chromosomal breakage analysis. Anemia. 2012;2012:238731. doi:10.1155/2012/238731.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Pinto N, Cohn SL, Dolan ME. Using germline genomics to individualize pediatric cancer treatments. Clin Cancer Res Off J Am Assoc Cancer Res. 2012;18(10):2791–800.

    Article  CAS  Google Scholar 

  49. Pollard JM, Gatti RA. Clinical radiation sensitivity with DNA repair disorders: an overview. Int J Radiat Oncol Biol Phys. 2009;74(5):1323–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Prasad R, Johnston LB, Savage MO, Martin L, Perry LA, Storr HL. Pediatric endocrine screening for von Hippel-Lindau disease: benefits and the challenge of compliance. J Endocrinol Invest. 2011;34(4):296–9.

    Article  CAS  PubMed  Google Scholar 

  51. Rahman N. Mechanisms predisposing to childhood overgrowth and cancer. Curr Opin Genet Dev. 2005;15(3):227–33.

    Article  CAS  PubMed  Google Scholar 

  52. Rahman N, Scott RH. Cancer genes associated with phenotypes in monoallelic and biallelic mutation carriers: new lessons from old players. Hum Mol Genet. 2007;16 Spec No(1):R60–6.

    Article  Google Scholar 

  53. Ricketts CJ, Forman JR, Rattenberry E, Bradshaw N, Lalloo F, Izatt L, Cole TR, et al. Tumor risks and genotype-phenotype-proteotype analysis in 358 patients with germline mutations in SDHB and SDHD. Hum Mutat. 2010;31(1):41–51.

    Article  CAS  PubMed  Google Scholar 

  54. Schaffer JV, Kamino H, Witkiewicz A, McNiff JM, Orlow SJ. Mucocutaneous neuromas: an underrecognized manifestation of PTEN hamartoma-tumor syndrome. Arch Dermatol. 2006;142(5):625–32.

    Article  PubMed  Google Scholar 

  55. Scott RH, Stiller CA, Walker L, Rahman N. Syndromes and constitutional chromosomal abnormalities associated with Wilms tumour. J Med Genet. 2006;43(9):705–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Scott RH, Walker L, Olsen ØE, Levitt G, Kenney I, Maher E, Owens CM, et al. Surveillance for Wilms tumour in at-risk children: pragmatic recommendations for best practice. Arch Dis Child. 2006;91(12):995–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Segers H, Kersseboom R, Alders M, Pieters R, Wagner A, Van den Heuvel-Eibrink MM. Frequency of WT1 and 11p15 constitutional aberrations and phenotypic correlation in childhood Wilms tumour patients. Eur J Cancer. 2012;48(17):3249–56.

    Article  CAS  PubMed  Google Scholar 

  58. Sévenet N, Sheridan E, Amram D, Schneider P, Handgretinger R, Delattre O. Constitutional mutations of the hSNF5/INI1 gene predispose to a variety of cancers. Am J Hum Genet. 1999;65(5):1342–8.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Slade I, Bacchelli C, Davies H, Murray A, Abbaszadeh F, Hanks S, Barfoot R, et al. DICER1 syndrome: clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition syndrome. J Med Genet. 2011;48(4):273–8.

    Article  CAS  PubMed  Google Scholar 

  60. Smith VV, Eng C, Milla PJ. Intestinal ganglioneuromatosis and multiple endocrine neoplasia type 2B: implications for treatment. Gut. 1999;45(1):143–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Snape K, Hanks S, Ruark E, Barros-Núñez P, Elliott A, Murray A, Lane AH, et al. Mutations in CEP57 cause mosaic variegated aneuploidy syndrome. Nat Genet. 2011;43(6):527–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Spigelman AD, Murday V, Phillips RK. Cancer and the Peutz-Jeghers syndrome. Gut. 1989;30(11):1588–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Spoudeas HAH, Harrison BJ. Paediatric endocrine tumours. West Sussex: Novo Nordisk Ltd.; 2005. p. 1–127.

    Google Scholar 

  64. Squire R, Bianchi A, Jakate SM. Radiation-induced sarcoma of the breast in a female adolescent. Case report with histologic and therapeutic considerations. Cancer. 1988;61(12):2444–7.

    Article  CAS  PubMed  Google Scholar 

  65. Stratakis CA, Schussheim DH, Freedman SM, Keil MF, Pack SD, Agarwal SK, Skarulis MC, et al. Pituitary macroadenoma in a 5-year-old: an early expression of multiple endocrine neoplasia type 1. J Clin Endocrinol Metab. 2000;85(12):4776–80.

    CAS  PubMed  Google Scholar 

  66. Tatton-Brown K, Hanks S, Ruark E. Germline mutations in the oncogene EZH2 cause Weaver syndrome and increased human height. Oncotarget. 2011;2(12):1127–33.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Taylor MD, Liu L, Raffel C, Hui C, Mainprize TG, Zhang X, Agatep R, et al. Mutations in SUFU predispose to medulloblastoma. Nat Genet. 2002;31(3):306–10.

    Article  CAS  PubMed  Google Scholar 

  68. Teplick A, Kowalski M, Biegel JA, Nichols KE. Educational paper: screening in cancer predisposition syndromes: guidelines for the general pediatrician. Eur J Pediatr. 2011;170(3):285–94.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Thakker RV. Multiple endocrine neoplasia type 1. Indian J Endocrinol Metab. 2012;16 Suppl 2:S272–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Varley JM. Germline TP53 mutations and Li-Fraumeni syndrome. Hum Mutat. 2003;21(3):313–20.

    Article  CAS  PubMed  Google Scholar 

  71. Villani A, Tabori U, Schiffman J, Shlien A, Beyene J, Druker H, Novokmet A, et al. Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: a prospective observational study. Lancet Oncol. 2011;12(6):559–67.

    Article  CAS  PubMed  Google Scholar 

  72. Zarate YA, Mena R, Martin LJ, Steele P, Tinkle BT, Hopkin RJ. Experience with hemihyperplasia and Beckwith-Wiedemann syndrome surveillance protocol. Am J Med Genet A. 2009;149A(8):1691–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Genetics, Southern General Hospital, Glasgow, Scotland, UK

    Victoria A. Murday BSc, FRCP

Authors
  1. Victoria A. Murday BSc, FRCP
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Victoria A. Murday BSc, FRCP .

Editor information

Editors and Affiliations

  1. Surgical Paediatrics, University of Glasgow, Glasgow, United Kingdom

    Robert Carachi

  2. Indianapolis, Indiana, USA

    Jay L. Grosfeld

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Murday, V.A. (2016). Screening for Genetic Susceptibility to Paediatric Tumours. In: Carachi, R., Grosfeld, J. (eds) The Surgery of Childhood Tumors. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-48590-3_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-48590-3_4

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-48588-0

  • Online ISBN: 978-3-662-48590-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation