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

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Abstract

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.

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Acknowledgements

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

Funding

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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Authors and Affiliations

  1. Hereditary Cancer Center, Creighton University, 202 Hixson-Lied Science Building, Omaha, NE, 68178, USA

    Henry T. Lynch, Stephen Lanspa, Trudy Shaw, Murray Joseph Casey, Mark Stacey & Carrie Snyder

  2. Gastrointestinal Division, Internal Medicine Department, Creighton University, Omaha, NE, 68178, USA

    Stephen Lanspa

  3. Department of Obstetrics and Gynecology, Creighton University, Omaha, NE, 68178, USA

    Murray Joseph Casey

  4. The Rose Salter Medical Research Foundation, 34 Versailles, Newport Coast, CA, 92657, USA

    Marc Rendell

  5. Internal Medicine Department, Creighton University, 2500 California Plaza, Omaha, NE, 68178, USA

    Theresa Townley

  6. Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Steven Spielberg Building Room 365, Los Angeles, CA, 90048, USA

    Megan Hitchins

  7. Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, 333 Cassell Drive, Suite 1200, Baltimore, MD, 21224, USA

    Joan Bailey-Wilson

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  1. Henry T. Lynch
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Correspondence to Henry T. Lynch.

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Lynch, H.T., Lanspa, S., Shaw, T. et al. Phenotypic and genotypic heterogeneity of Lynch syndrome: a complex diagnostic challenge. Familial Cancer 17, 403–414 (2018). https://doi.org/10.1007/s10689-017-0053-3

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