TSPAN8
Overview
TSPAN8 (Tetraspanin 8) encodes a member of the tetraspanin superfamily, transmembrane scaffold proteins that organise signalling complexes at the cell surface. TSPAN8 is implicated in tumour progression, angiogenesis, and metastasis through regulation of cell adhesion and exosome biology.
Alterations observed in the corpus
- Non-silent TSPAN8 mutation marks the primary-to-metastasis transition at divergence node 5 in the WCM117 rapid-autopsy phylogeny of urothelial carcinoma (BLCA); proposed as a candidate metastasis-initiating event given TSPAN8’s known pro-metastatic and angiogenesis-promoting roles. PMID:27749842
Cancer types (linked)
- Bladder urothelial carcinoma (BLCA): TSPAN8 mutation observed at the clonal transition from primary to distant metastases in one patient (WCM117) in a 72-tumour WES cohort enriched for advanced disease. PMID:27749842
Co-occurrence and mutual exclusivity
- In the WCM117 rapid-autopsy case, TSPAN8 mutation was absent from the untreated TURBT primary and appeared in the metastatic lineage at divergence node 5, co-occurring with CDKN2A homozygous deletion that evolved from a sub-clonal heterozygous deletion. PMID:27749842
Therapeutic relevance
- No targeted therapy identified. TSPAN8’s role in exosome-mediated signalling and angiogenesis makes it a candidate biomarker for metastatic progression, but no clinical interventions have been evaluated.
Open questions
- The metastasis-driver role of TSPAN8 in WCM117 is inferred from a single rapid-autopsy case; prospective functional studies and independent cohort validation are lacking. PMID:27749842
Sources
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