Immunogenomic Biomarkers and Validation in Lynch Syndrome

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.

Automated summary

Lynch syndrome is a hereditary disorder with increased risk of colorectal and non-colorectal cancers. Mutations in DNA repair genes lead to dysfunctional post-replication repair system and production of neoantigens, triggering an immune response. Due to invasive nature of screening tests, adherence to cancer screening guidelines among Lynch variant heterozygotes is poor. The potential of immunogenomic biomarkers in Lynch syndrome and their correlation with cancer onset and stage is currently unclear.