New RPS20 gene variant in colorectal cancer diagnosis: insight from a large series of patients.

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• Germline pathogenic variants in RPS20 (ribosomal protein S20) are implicated in hereditary colorectal cancer (CRC) predisposition, particularly in cases lacking DNA mismatch repair deficiency.
• RPS20 variants are exceedingly rare, with only five previously reported cases in scientific literature.

Purpose of the Study:

• To investigate the role of RPS20 germline variants in patients with a history suggestive of hereditary CRC predisposition.
• To identify and characterize novel RPS20 pathogenic variants associated with colorectal cancer.

Main Methods:

• Retrospective germline analysis of the RPS20 gene in 1035 consecutive patients with suspected hereditary CRC.
• Genetic variant identification and characterization, including loss-of-function and de novo variants.

Main Results:

• A pathogenic RPS20 loss-of-function variant (NM_001146227.1:c.115_116del, p.(Leu39Aspfs*33)) was identified in one patient.
• This frameshift variant is the first reported de novo RPS20 variant in CRC, found in a 35-year-old female diagnosed with rectal cancer, multiple adenomatous polyps, and breast cancer.
• Known pathogenic variants in other CRC genes were identified in 15% of the patient cohort.

Conclusions:

• The RPS20 gene plays a complex role in oncogenesis, potentially acting as an oncogene or tumor suppressor.
• The rarity of RPS20 variants necessitates further data collection to define the associated cancer phenotypic spectrum and improve genetic counseling and patient management.
• RPS20 variants are associated with Diamond-Blackfan anemia, highlighting the gene's multifaceted clinical relevance.