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

Henry T Lynch; Stephen Lanspa; Trudy Shaw; Murray Joseph Casey; Marc Rendell; Mark Stacey; Theresa Townley; Carrie Snyder; Megan Hitchins; Joan Bailey-Wilson

doi:10.1007/s10689-017-0053-3

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

Fam Cancer. 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. [email protected].
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.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Colorectal Neoplasms, Hereditary Nonpolyposis / diagnosis*
Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
Colorectal Neoplasms, Hereditary Nonpolyposis / pathology
Genotype
Humans
Phenotype

Grants and funding

LB595/Nebraska Department of Health and Human Services/International