MCM8&9 - Jun 2022

Project title:
Role of MCM8/9 variants in (colorectal) cancer predisposition

Project leader:
Maartje Nielsen, Leiden University Medical Centre, Leiden, the Netherlands

Project Description:
MCM8 (Minichromosome Maintenance 8 Homologous Recombination Repair Factor) and MCM9 (Minichromosome Maintenance 9 Homologous Recombination Repair Factor) encode for a helicase hexameric protein complex involved in multiple DNA repair mechanisms, including genome maintenance, meiotic recombination, homologous recombination and mismatch repair. Bi-allelic pathogenic variants of MCM8/9 have been widely associated with primary ovarian insufficiency and were recently reported in a limited number of patients with (colorectal) cancer and polyposis.

Our goal is to further explore the potential role of MCM8/9 variants in (colorectal) cancer predisposition. Therefore, this study aims (i) to investigate the molecular profile and mutational signatures of tumors from bi-allelic MCM8/9 carriers using whole-genome-sequencing, and (ii) to describe cancer aggregation in new families with bi-allelic MCM8/9 variants. For this, we would like to get in contact with clinicians and researchers known with bi-allelic MCM8/9 carriers, to see whether they have any follow-up data regarding the development of cancer and whether collaboration is possible.

Both GENTURIS and non-GENTURIS members are welcome to participate. 3 ERN GENTURIS centres have contributed already.

Start date: June 2022

Duration: 1 year

Funder: --