Review

. 2018 Jul;17(3):403-414.

doi: 10.1007/s10689-017-0053-3.

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

Henry T Lynch¹, Stephen Lanspa^{2

3}, Trudy Shaw², Murray Joseph Casey^{2

4}, Marc Rendell⁵, Mark Stacey², Theresa Townley⁶, Carrie Snyder², Megan Hitchins⁷, Joan Bailey-Wilson⁸

Affiliations

¹ Hereditary Cancer Center, Creighton University, 202 Hixson-Lied Science Building, Omaha, NE, 68178, USA. htlynch@creighton.edu.
² Hereditary Cancer Center, Creighton University, 202 Hixson-Lied Science Building, Omaha, NE, 68178, USA.
³ Gastrointestinal Division, Internal Medicine Department, Creighton University, Omaha, NE, 68178, USA.
⁴ Department of Obstetrics and Gynecology, Creighton University, Omaha, NE, 68178, USA.
⁵ The Rose Salter Medical Research Foundation, 34 Versailles, Newport Coast, CA, 92657, USA.
⁶ Internal Medicine Department, Creighton University, 2500 California Plaza, Omaha, NE, 68178, USA.
⁷ Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Steven Spielberg Building Room 365, Los Angeles, CA, 90048, USA.
⁸ Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, 333 Cassell Drive, Suite 1200, Baltimore, MD, 21224, USA.

PMID: 29071502
DOI: 10.1007/s10689-017-0053-3

Review

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

Henry T Lynch et al. Fam Cancer. 2018 Jul.

. 2018 Jul;17(3):403-414.

doi: 10.1007/s10689-017-0053-3.

Authors

Henry T Lynch¹, Stephen Lanspa^{2

3}, Trudy Shaw², Murray Joseph Casey^{2

4}, Marc Rendell⁵, Mark Stacey², Theresa Townley⁶, Carrie Snyder², Megan Hitchins⁷, Joan Bailey-Wilson⁸

Affiliations

¹ Hereditary Cancer Center, Creighton University, 202 Hixson-Lied Science Building, Omaha, NE, 68178, USA. htlynch@creighton.edu.
² Hereditary Cancer Center, Creighton University, 202 Hixson-Lied Science Building, Omaha, NE, 68178, USA.
³ Gastrointestinal Division, Internal Medicine Department, Creighton University, Omaha, NE, 68178, USA.
⁴ Department of Obstetrics and Gynecology, Creighton University, Omaha, NE, 68178, USA.
⁵ The Rose Salter Medical Research Foundation, 34 Versailles, Newport Coast, CA, 92657, USA.
⁶ Internal Medicine Department, Creighton University, 2500 California Plaza, Omaha, NE, 68178, USA.
⁷ Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Steven Spielberg Building Room 365, Los Angeles, CA, 90048, USA.
⁸ Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, 333 Cassell Drive, Suite 1200, Baltimore, MD, 21224, USA.

PMID: 29071502
DOI: 10.1007/s10689-017-0053-3

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.

Keywords: Colorectal cancer; Endometrial cancer; Hereditary cancer; Hereditary nonpolyposis colorectal cancer; Lynch syndrome; Mismatch repair.

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References

1. Ann Med. 1996 Dec;28(6):479-82 - PubMed
1. Cancer Prev Res (Phila). 2008 Nov;1(6):470-5 - PubMed
1. Hum Mutat. 2009 Feb;30(2):197-203 - PubMed
1. Anticancer Res. 2016 Sep;36(9):4399-405 - PubMed
1. Transl Res. 2009 Dec;154(6):277-87 - PubMed

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

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

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