Immunogenomic Biomarkers and Validation in Lynch Syndrome

Ramadhani Chambuso; Mbali Mthembu; Eveline Kaambo; Barbara Robertson; Raj Ramesar

doi:10.3390/cells12030491

Immunogenomic Biomarkers and Validation in Lynch Syndrome

Cells. 2023 Feb 2;12(3):491. doi: 10.3390/cells12030491.

Authors

Ramadhani Chambuso¹, Mbali Mthembu¹, Eveline Kaambo^{2

3}, Barbara Robertson⁴, Raj Ramesar¹

Affiliations

¹ MRC Unit for Genomic and Precision Medicine, Division of Human Genetics, Department of Pathology, Institute for Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory, Cape Town 7704, South Africa.
² Department of Biochemistry and Medical Microbiology, School of Medicine, University of Namibia, 340, Windhoek 9000, Namibia.
³ Division of Medical Virology, Department of Pathology, Institute for Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7704, South Africa.
⁴ Department of Radiation Oncology, Groote Schuur Hospital, University of Cape Town, Observatory, Cape Town 7704, South Africa.

Abstract

Lynch syndrome (LS) is an inherited disorder in which affected individuals have a significantly higher-than-average risk of developing colorectal and non-colorectal cancers, often before the age of 50 years. In LS, mutations in DNA repair genes lead to a dysfunctional post-replication repair system. As a result, the unrepaired errors in coding regions of the genome produce novel proteins, called neoantigens. Neoantigens are recognised by the immune system as foreign and trigger an immune response. Due to the invasive nature of cancer screening tests, universal cancer screening guidelines unique for LS (primarily colonoscopy) are poorly adhered to by LS variant heterozygotes (LSVH). Currently, it is unclear whether immunogenomic components produced as a result of neoantigen formation can be used as novel biomarkers in LS. We hypothesise that: (i) LSVH produce measurable and dynamic immunogenomic components in blood, and (ii) these quantifiable immunogenomic components correlate with cancer onset and stage. Here, we discuss the feasibility to: (a) identify personalised novel immunogenomic biomarkers and (b) validate these biomarkers in various clinical scenarios in LSVH.

Keywords: Lynch syndrome variant heterozygotes; colorectal and non-colorectal cancers; frameshift mutations; immune responses; immunogenomic biomarkers; neoantigens.

Publication types

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

MeSH terms

Biomarkers
Colorectal Neoplasms, Hereditary Nonpolyposis* / diagnosis
Colorectal Neoplasms, Hereditary Nonpolyposis* / genetics
Endometrial Neoplasms* / genetics
Female
Germ-Line Mutation
Humans
Middle Aged

Substances

Biomarkers

Grants and funding

This research was funded by South Africa Department of Science and Innovation to the Medical Research Council, grant number MRC415621/UCT and the APC was funded by the University of Cape Town.