RPS20 - Sep 2025

Project title:
Characterization of RPS20 germline variants in early-onset colorectal cancer families

Project leaders:

Maartje Nielsen (m.nielsen@lumc.nl) & Noah Helderman (n.c.helderman@lumc.nl), Clinical Genetics, Leiden University Medical Centre, Leiden, the Netherlands
PhD student on the project: Salwa Ben Yahia (s.ben_yahia@lumc.nl), Clinical Genetics, Leiden University Medical Centre, Leiden, the Netherlands

Project Description:

Pathogenic variants in RPS20 have been linked to early-onset, highly penetrant, MMR-proficient colorectal (CRC) tumors, establishing it as a distinct and clinically significant CRC susceptibility gene. RPS20 encodes the uS10, a component of the 40S ribosomal subunit essential for ribosome maturation. Its biological role in CRC tumorigenesis is hypothesized to stem from its critical function in ribosome biogenesis and protein synthesis, which may influence cellular proliferation and genome stability.

We aim to further explore the role of RPS20 variants in cancer predisposition by:

Investigating the molecular profiles and mutational signatures of tumors from patients harboring germline RPS20 variants.
Describing cancer aggregation patterns and clinical phenotypes in families with pathogenic RPS20 variants.
Assessing the impact of RPS20 dysfunction on ribosome biogenesis and tumor suppressor pathways such as p53 signaling.

We are seeking to connect with clinicians and researchers who have identified patients or families carrying pathogenic or likely pathogenic variants in RPS20. Whether you have follow-up data on cancer development and tumor characterization or have performed functional analyses related to RPS20, we would be eager to collaborate and share resources or data.
Both ERN GENTURIS members and non-members are welcome to participate.

Start date: Sep 2025

Duration: 1 year

Funder: -