Salvador Jaime-Casas: Comparative Genomic Characterization of SCBC With Urothelial Carcinoma and SCLC
Salvador Jaime-Casas, Postdoc Fellow at City of Hope, shared on X:
” Thrilled to share our new publication in JCO Precision Oncology. Led by Abhishek Tripathi, Neal S. Chawla, Nick Salgia at City of Hope, we conducted a comparative genomic analysis of small cell bladder cancer (SCBC), evaluating its mutational landscape relative to urothelial carcinoma (UC) and small cell lung cancer (SCLC).
Authors: Salvador Jaime-Casas et al.
We analyzed 149 SCBC, 4,350 UC, and 1,697 SCLC patients.
Key findings:
- SCBC primarily harbored mutations in TP53 (87%), TERT (75%), and RB1 (70%).
- Among SCBC patients with TP53 mutations, 77% also had RB1 commutations.
- Overall, SCBC shared genomic features with both UC and SCLC.
Exploring co-occurrence patterns:
- The most frequent co-mutations with TP53 were TERT (83%) and RB1 (77%).
- TERT mutations commonly co-occurred with RB1 (79%) and ARID1A (40%).
Importantly, mutation prevalence was comparable between tissue-based and blood-based sequencing:
TP53 (95.9%), TERT (81.0%), RB1 (74.3%), ARID1A (21.6%), CDKN1A (17.5%).
Comparison to SCLC:
- TP53 (87.3% vs 88.3%; P = 0.79), RB1 (69.8% vs 67.2%; P = 0.57), and PTEN (11.4% vs 12.1%; P = 0.89) mutation rates were similar between SCBC and SCLC.
- However, TERT mutations were almost exclusive to SCBC (75.2% vs 6.2%; P < 0.0001).
We identified clinically actionable targets in SCBC and highlighted relevant ongoing trials:
- FGFR alterations (14%) → Potential role for pan-FGFR inhibitors.
- HER2 (ERBB2) alterations (12.6%) → HER2-targeted ADCs could show therapeutic efficacy.
- NOTCH 1–4 alterations → Lurbinectedin, a NOTCH-modulator drug, has shown efficacy in SCLC and may offer promise here, too. A foundation for future biomarker-driven therapies!
In summary, SCBC demonstrates:
- A hybrid genomic identity (neuroendocrine + urothelial features)
- Frequent, targetable alterations
- Opportunities for precision oncology approaches.
Proud to be part of this incredible work developed by stellar team at City of Hope.
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