Familial Cancer

, Volume 17, Issue 3, pp 403–414 | Cite as

Phenotypic and genotypic heterogeneity of Lynch syndrome: a complex diagnostic challenge

  • Henry T. LynchEmail author
  • Stephen Lanspa
  • Trudy Shaw
  • Murray Joseph Casey
  • Marc Rendell
  • Mark Stacey
  • Theresa Townley
  • Carrie Snyder
  • Megan Hitchins
  • Joan Bailey-Wilson


Lynch syndrome is the hereditary disorder that most frequently predisposes to colorectal cancer as well as predisposing to a number of extracolonic cancers, most prominently endometrial cancer. It is caused by germline mutations in the mismatch repair genes. Both its phenotype and genotype show marked heterogeneity. This review gives a historical overview of the syndrome, its heterogeneity, its genomic landscape, and its implications for complex diagnosis, genetic counseling and putative implications for immunotherapy.


Lynch syndrome Hereditary nonpolyposis colorectal cancer Hereditary cancer Mismatch repair Colorectal cancer Endometrial cancer 



We thank Peter Silberstein, M.D., for technical assistance.


This work was supported by revenue from Nebraska’s excise tax on cigarettes awarded to Creighton University by the Nebraska Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the State of Nebraska or the Nebraska Department of Health and Human Services. Funding was also received from the Liz’s Legacy fund through Kicks for a Cure. Dr. Henry Lynch’s work is partially funded through the Charles F. and Mary C. Heider Chair in Cancer Research, which he holds at Creighton University.


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Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  • Henry T. Lynch
    • 1
    Email author
  • Stephen Lanspa
    • 1
    • 2
  • Trudy Shaw
    • 1
  • Murray Joseph Casey
    • 1
    • 3
  • Marc Rendell
    • 4
  • Mark Stacey
    • 1
  • Theresa Townley
    • 5
  • Carrie Snyder
    • 1
  • Megan Hitchins
    • 6
  • Joan Bailey-Wilson
    • 7
  1. 1.Hereditary Cancer CenterCreighton UniversityOmahaUSA
  2. 2.Gastrointestinal Division, Internal Medicine DepartmentCreighton UniversityOmahaUSA
  3. 3.Department of Obstetrics and GynecologyCreighton UniversityOmahaUSA
  4. 4.The Rose Salter Medical Research FoundationNewport CoastUSA
  5. 5.Internal Medicine DepartmentCreighton UniversityOmahaUSA
  6. 6.Department of Biomedical SciencesCedars-Sinai Medical CenterLos AngelesUSA
  7. 7.Computational and Statistical Genomics Branch, National Human Genome Research InstituteNational Institutes of HealthBaltimoreUSA

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