LSS
Overview
LSS (Lanosterol Synthase) encodes a key enzyme in the cholesterol biosynthesis pathway, catalyzing the cyclization of (S)-2,3-oxidosqualene to lanosterol. It has been observed with sub-clonal somatic mutations in urothelial carcinoma clonal evolution studies, suggesting possible roles in metabolic reprogramming under therapeutic selection pressure, though its precise oncogenic function remains poorly characterized.
Alterations observed in the corpus
- Sub-clonal mutation in the WCM117 urothelial carcinoma (UC) rapid-autopsy patient’s primary tumor that became clonally enriched in chemotherapy-treated metastatic lesions (early founder signal that survived platinum-based chemotherapy selection); identified alongside RYR2, ANKRD62, and NCOA3 as mutations exhibiting this enrichment pattern in the 32-patient matched pre/post-chemotherapy WES cohort. PMID:27749842
Cancer types (linked)
- BLCA: Observed as a sub-clonal mutation in primary UC that was clonally enriched in post-chemotherapy metastatic lesions; context suggests possible chemotherapy-selection advantage, though the functional basis is not established. PMID:27749842
Co-occurrence and mutual exclusivity
- Found alongside RYR2, ANKRD62, and NCOA3 as sub-clonal mutations in the WCM117 primary that were enriched in chemotherapy-treated metastases; no broader co-occurrence patterns reported. PMID:27749842
Therapeutic relevance
- No direct therapeutic relevance established. Clonal enrichment under platinum-based chemotherapy selection warrants further investigation of LSS and cholesterol-pathway alterations in chemotherapy-resistant UC. PMID:27749842
Open questions
- Whether LSS mutations confer a growth or survival advantage under platinum-based chemotherapy (or are enriched by neutral drift) is unresolved. Functional studies are absent from the citing report. PMID:27749842
Sources
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