Skip to main content
SpringerLink
Log in
Book cover

Molecular Pathology in Clinical Practice pp 329–337Cite as

Familial Adenomatous Polyposis and Turcot and Peutz–Jeghers Syndromes

  • Chapter

  • 3560 Accesses

Abstract

To date the majority of colorectal cancers are thought to be sporadic. However, familial predisposition has been well recognized for years. Familial adenomatous polyposis coli, Turcot syndrome, Gardner syndrome, and Peutz–Jeghers syndrome are examples of hereditary syndromes that predispose individuals to colorectal adenocarcinoma as well as a host of other malignant, hamartomatous, and benign growths. While not comprehensive of all familial colorectal predisposition syndromes, a summary of these syndromes is provided in this chapter.

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   89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
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. Bulow S, Faurschou Nielsen T, Bulow C, Bisgaard ML, Karlsen L, Moesgaard F. The incidence rate of familial adenomatous polyposis. Results from the Danish Polyposis Register. Int J Colorectal Dis. 1996;11:88–91.

    Article  CAS  PubMed  Google Scholar 

  2. Jarvinen HJ. Epidemiology of familial adenomatous polyposis in Finland: impact of family screening on colorectal cancer rate and survival. Gut. 1992;1992(33):357–60.

    Article  Google Scholar 

  3. American Gastroenterology Association. AGA technical review on hereditary colorectal cacner and genetic testing. Gastroenterology. 2001;121:198–213.

    Article  Google Scholar 

  4. Gardner EJ. A genetic and clinical study of intestinal polyposis, a predisposing factor for carcinoma of the colon and rectum. Am J Hum Genet. 1951;3:167–76.

    PubMed Central  CAS  PubMed  Google Scholar 

  5. Turcot J, Despres JP, St Pierre F. Malignant tumors of the central nervous system associated with familial polyposis of the colon: report of two cases. Dis Colon Rectum. 1959;2:465–8.

    Article  CAS  PubMed  Google Scholar 

  6. Kinzler KW, Nilbert MC, Su LK, Vogelstein B, Bryan TM, Levy DB, et al. Identification of FAP locus genes from chromosome 5q21. Science. 1991;253:661–5.

    Article  CAS  PubMed  Google Scholar 

  7. Jarrar AM, Milas M, Mitchell J, Laguardia L, O'Malley M, Berber E, et al. Screening for thyroid cancer in patients with familial adenomatous polyposis. Ann Surg. 2011;253:515–21. doi:10.1097/SLA.0b013e3181fcba8a.

    Article  PubMed  Google Scholar 

  8. Harach HR, Williams GT, Williams ED. Familial adenomatous polyposis associated thyroid carcinoma: a distinct type of follicular cell neoplasm. Histopathology. 1994;25:549–61.

    Article  CAS  PubMed  Google Scholar 

  9. Nose V. Thyroid cancer of follicular cell origin in inherited tumor syndromes. Adv Anat Pathol. 2010;17:428–36. doi:10.1097/PAP.0b013e3181f8b028.

    Article  CAS  PubMed  Google Scholar 

  10. Hamilton SR, Liu B, Parsons RE, Papadopoulos N, Jen J, Powell SM, et al. The molecular basis of Turcot’s syndrome. N Engl J Med. 1995;332:839–47. doi:10.1056/NEJM199503303321302.

    Article  CAS  PubMed  Google Scholar 

  11. Fallen T, Wilson M, Morlan B, Lindor NM. Desmoid tumors—a characterization of patients seen at Mayo Clinic 1976–1999. Fam Cancer. 2006;5:191–4. doi:10.1007/s10689-005-5959-5.

    Article  PubMed  Google Scholar 

  12. Gardner EJ, Richards RC. Multiple cutaneous and subcutaneous lesions occurring simultaneously with hereditary polyposis and osteomatosis. Am J Hum Genet. 1953;5:139–47.

    PubMed Central  CAS  PubMed  Google Scholar 

  13. Spirio L, Olschwang S, Groden J, Robertson M, Samowitz W, Joslyn G, et al. Alleles of the APC gene: an attenuated form of familial polyposis. Cell. 1993;75:951–7.

    Article  CAS  PubMed  Google Scholar 

  14. Knudsen AL, Bisgaard ML, Bulow S. Attenuated familial adenomatous polyposis (AFAP). A review of the literature. Fam Cancer. 2003;2:43–55.

    Article  PubMed  Google Scholar 

  15. Alkhouri N, Franciosi JP, Mamula P. Familial adenomatous polyposis in children and adolescents. J Pediatr Gastroenterol Nutr. 2010;51:727–32. doi:10.1097/MPG.0b013e3181e1a224.

    Article  PubMed  Google Scholar 

  16. Parc Y, Piquard A, Dozois RR, Parc R, Tiret E. Long-term outcome of familial adenomatous polyposis patients after restorative coloproctectomy. Ann Surg. 2004;239:378–82.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Al-Sukhni W, Aronson M, Gallinger S. Hereditary colorectal cancer syndromes: familial adenomatous polyposis and lynch syndrome. Surg Clin North Am. 2008;88(4):819–844 vii. doi:10.1016/j.suc.2008.04.012.

    Article  PubMed  Google Scholar 

  18. Latchford A, Volikos E, Johnson V, Rogers P, Suraweera N, Tomlinson I, et al. APC mutations in FAP-associated desmoid tumours are non-random but not ‘just right’. Hum Mol Genet. 2007;16:78–82. doi:10.1093/hmg/ddl442.

    Article  CAS  PubMed  Google Scholar 

  19. Nieuwenhuis MH, Mathus-Vliegen EM, Baeten CG, Nagengast FM, van der Bijl J, van Dalsen AD, et al. Evaluation of management of desmoid tumours associated with familial adenomatous polyposis in Dutch patients. Br J Cancer. 2011;104:37–42. doi:10.1038/sj.bjc.6605997.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Robson ME, Storm CD, Weitzel J, Wollins DS, Offit K. American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. J Clin Oncol. 2010;28:893–901. doi:10.1200/JCO.2009.27.0660.

    Article  PubMed  Google Scholar 

  21. Lefevre JH, Rodrigue CM, Mourra N, Bennis M, Flejou JF, Parc R, et al. Implication of MYH in colorectal polyposis. Ann Surg. 2006;244:874–9. doi:10.1097/01.sla.0000246937.54435.50. discussion 879-880.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Soravia C, Berk T, Madlensky L, Mitri A, Cheng H, Gallinger S, et al. Genotype-phenotype correlations in attenuated adenomatous polyposis coli. Am J Hum Genet. 1998;62:1290–301. doi:10.1086/301883.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Wallis YL, Morton DG, McKeown CM, Macdonald F. Molecular analysis of the APC gene in 205 families: extended genotype-phenotype correlations in FAP and evidence for the role of APC amino acid changes in colorectal cancer predisposition. J Med Genet. 1999;36:14–20.

    PubMed Central  CAS  PubMed  Google Scholar 

  24. Sieber OM, Tomlinson IP, Lamlum H. The adenomatous polyposis coli (APC) tumor suppressor -genetics, function and disease. Mol Med Today. 2000;6:462–9.

    Article  CAS  PubMed  Google Scholar 

  25. Laken SJ, Petersen GM, Gruber SB, Oddoux C, Ostrer H, Giardiello FM, et al. Familial colorectal cancer in Ashkenazim due to a hypermutable tract in APC. Nat Genet. 1997;17:79–83. doi:10.1038/ng0997-79.

    Article  CAS  PubMed  Google Scholar 

  26. Kerr SE, Thomas CB, Thibodeau SN, Ferber MJ, Halling KC. APC germline mutations in individuals being evaluated for familial adenomatous polyposis: a review of the Mayo Clinic experience with 1591 consecutive tests. J Mol Diagn. 2013;15:31–43.

    Article  CAS  PubMed  Google Scholar 

  27. Nielsen M, Bik E, Hes FJ, Breuning MH, Vasen HF, Bakker E, et al. Genotype-phenotype correlations in 19 Dutch cases with APC gene deletions and a literature review. Eur J Hum Genet. 2007;15:1034–42. doi:10.1038/sj.ejhg.5201871.

    Article  CAS  PubMed  Google Scholar 

  28. Friedl W, Caspari R, Sengteller M, Uhlhaas S, Lamberti C, Jungck M, et al. Can APC mutation analysis contribute to therapeutic decisions in familial adenomatous polyposis? Experience from 680 FAP families. Gut. 2001;48:515–21.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Westerman AM, Entius MM, de Baar E, Boor PP, Koole R, van Velthuysen ML, et al. Peutz-Jeghers syndrome: 78-year follow-up of the original family. Lancet. 1999;353:1211–5.

    Article  CAS  PubMed  Google Scholar 

  30. Jeghers H, Mc KV, Katz KH. Generalized intestinal polyposis and melanin spots of the oral mucosa, lips and digits; a syndrome of diagnostic significance. N Engl J Med. 1949;241:1031–6. doi:10.1056/NEJM194912292412601.

    Article  CAS  PubMed  Google Scholar 

  31. Hamilton SR, Aaltonen LA. Pathology and genetics of tumours of the digestive system. In: Kleihues P, Sobin LH, editors. World Health Organization classification of tumours. Lyon, France: IARC Press; 2000. p. 251.

    Google Scholar 

  32. Giardiello FM, Brensinger JD, Tersmette AC, Goodman SN, Petersen GM, Booker SV, et al. Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology. 2000;119:1447–53.

    Article  CAS  PubMed  Google Scholar 

  33. van Lier MG, Wagner A, Mathus-Vliegen EM, Kuipers EJ, Steyerberg EW, van Leerdam ME. High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance recommendations. Am J Gastroenterol. 2010;105:1258–64. doi:10.1038/ajg.2009.725. author reply 1265.

    Article  PubMed  Google Scholar 

  34. Hearle N, Schumacher V, Menko FH, Olschwang S, Boardman LA, Gille JJ, et al. Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res. 2006;12:3209–15. doi:10.1158/1078-0432.CCR-06-0083.

    Article  CAS  PubMed  Google Scholar 

  35. Jass JR, Williams CB, Bussey HJ, Morson BC. Juvenile polyposis–a precancerous condition. Histopathology. 1988;13:619–30.

    Article  CAS  PubMed  Google Scholar 

  36. McCarthy PM, Piehler JM, Schaff HV, Pluth JR, Orszulak TA, Vidaillet Jr HJ, et al. The significance of multiple, recurrent, and “complex” cardiac myxomas. J Thorac Cardiovasc Surg. 1986;91:389–96.

    CAS  PubMed  Google Scholar 

  37. van Lier MG, Westerman AM, Wagner A, Looman CW, Wilson JH, de Rooij FW, et al. High cancer risk and increased mortality in patients with Peutz-Jeghers syndrome. Gut. 2011;60:141–7. doi:10.1136/gut.2010.223750.

    Article  PubMed  Google Scholar 

  38. Beggs AD, Latchford AR, Vasen HF, Moslein G, Alonso A, Aretz S, et al. Peutz-Jeghers syndrome: a systematic review and recommendations for management. Gut. 2010;59:975–86. doi:10.1136/gut.2009.198499.

    Article  CAS  PubMed  Google Scholar 

  39. Wei C, Amos CI, Zhang N, Wang X, Rashid A, Walker CL, et al. Suppression of Peutz-Jeghers polyposis by targeting mammalian target of rapamycin signaling. Clin Cancer Res. 2008;14:1167–71. doi:10.1158/1078-0432.CCR-07-4007.

    Article  CAS  PubMed  Google Scholar 

  40. Hemminki A, Markie D, Tomlinson I, Avizienyte E, Roth S, Loukola A, et al. A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature. 1998;391:184–7. doi:10.1038/34432.

    Article  CAS  PubMed  Google Scholar 

  41. Jenne DE, Reimann H, Nezu J, Friedel W, Loff S, Jeschke R, et al. Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet. 1998;18:38–43. doi:10.1038/ng0198-38.

    Article  CAS  PubMed  Google Scholar 

  42. Volikos E, Robinson J, Aittomaki K, Mecklin JP, Jarvinen H, Westerman AM, et al. LKB1 exonic and whole gene deletions are a common cause of Peutz-Jeghers syndrome. J Med Genet. 2006;43, e18. doi:10.1136/jmg.2005.039875.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Aretz S, Stienen D, Uhlhaas S, Loff S, Back W, Pagenstecher C, et al. High proportion of large genomic STK11 deletions in Peutz-Jeghers syndrome. Hum Mutat. 2005;26:513–9. doi:10.1002/humu.20253.

    Article  CAS  PubMed  Google Scholar 

  44. Mehenni H, Gehrig C, Nezu J, Oku A, Shimane M, Rossier C, et al. Loss of LKB1 kinase activity in Peutz-Jeghers syndrome, and evidence for allelic and locus heterogeneity. Am J Hum Genet. 1998;63:1641–50.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Tiainen M, Vaahtomeri K, Ylikorkala A, Makela TP. Growth arrest by the LKB1 tumor suppressor: induction of p21(WAF1/CIP1). Hum Mol Genet. 2002;11:1497–504.

    Google Scholar 

  46. Karuman P, Gozani O, Odze RD, Zhou XC, Zhu H, Shaw R, et al. The Peutz-Jegher gene product LKB1 is a mediator of p53-de pendent cell death. Mol Cell. 2001;7:1307–19.

    Google Scholar 

  47. Morton DG, Roos JM, Kemphues KJ. par-4, a gene required for cytoplasmic localization and determination of specific cell types in Caenorhabditis elegans embryogenesis. Genetics. 1992;130:771–90.

    PubMed Central  CAS  PubMed  Google Scholar 

  48. Alessi DR, Sakamoto K, Bayascas JR. LKB1-dependent signaling pathways. Annu Rev Biochem. 2006;75:137–63. doi:10.1146/annurev.biochem.75.103004.142702.

    Article  CAS  PubMed  Google Scholar 

  49. Lin-Marq N, Borel C, Antonarakis SE. Peutz-Jeghers LKB1 mutants fail to activate GSK-3beta, preventing it from inhibiting Wnt signaling. Mol Genet Genomics. 2005;273:184–96. doi:10.1007/s00438-005-1124-y.

    Article  CAS  PubMed  Google Scholar 

  50. Corradetti MN, Inoki K, Bardeesy N, DePinho RA, Guan KL. Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome. Genes Dev. 2004;18:1533–8. doi:10.1101/gad.1199104.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Mehenni H, Resta N, Guanti G, Mota-Vieira L, Lerner A, Peyman M, et al. Molecular and clinical characteristics in 46 families affected with Peutz-Jeghers syndrome. Dig Dis Sci. 2007;52:1924–33. doi:10.1007/s10620-006-9435-3.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Laboratory Medicine and Pathology, Laboratory Genetics, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Kandelaria M. Rumilla M.D.

Authors
  1. Kandelaria M. Rumilla M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kandelaria M. Rumilla M.D. .

Editor information

Editors and Affiliations

  1. Pathology and Laboratory Medicine, University of Vermont College of Medicine and University of Vermont Medical Center, Burlington, Vermont, USA

    Debra G.B. Leonard

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Rumilla, K.M. (2016). Familial Adenomatous Polyposis and Turcot and Peutz–Jeghers Syndromes. In: Leonard, D. (eds) Molecular Pathology in Clinical Practice. Springer, Cham. https://doi.org/10.1007/978-3-319-19674-9_23

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-19674-9_23

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-19673-2

  • Online ISBN: 978-3-319-19674-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation