RPS15
Overview
RPS15 encodes the 40S ribosomal subunit protein S15. Recurrent missense mutations in the C-terminal region were identified as a novel CLL driver in a large-scale whole-exome sequencing study, representing the first report of RPS15 mutation in human cancer. Mutations cluster at highly conserved positions (94/100 conservation score) and are associated with adverse clinical outcome in patients receiving frontline chemoimmunotherapy.
Alterations observed in the corpus
- Recurrent missense mutations in the C-terminal region in 4.3% (n=23) of CLL patients (conservation 94/100); novel CLL driver, not previously reported in human cancer; associated with shorter PFS (Bonferroni P = 0.024); component of the 40S ribosomal subunit PMID:26466571
Cancer types (linked)
- CLLSLL — Novel driver with 4.3% mutation frequency; independent predictor of shorter PFS on frontline fludarabine/cyclophosphamide ± rituximab (CLL8 trial) PMID:26466571
Co-occurrence and mutual exclusivity
- Co-occurs with other CLL drivers in the context of clonal evolution; presence of any subclonal driver (including RPS15) predicts shorter PFS in both FC and FCR arms (HR 1.6) PMID:26466571
Therapeutic relevance
- RPS15 mutation is an independent prognostic biomarker in chemoimmunotherapy (fludarabine/cyclophosphamide ± rituximab); no targeted therapy reported PMID:26466571
Open questions
- Mechanism by which ribosomal protein mutations drive CLL progression is unresolved; functional consequences of C-terminal missense variants need experimental validation PMID:26466571
Sources
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