201: Sex, Smoking, and Somatic Selection in the Bladder

Music:
Enjoy the music based on this article at the end of the episode.

DOI:
10.1038/s41586-025-09521-x

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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️ Episode:
201: 201: Sex, Smoking, and Somatic Selection in the Bladder

️ Season:
1

Article title:
Sex and smoking bias in the selection of somatic mutations in human bladder

Journal:
Nature

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-11-17.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Substantively audited transcript sections describing the sequencing approach, gene panel, positive/negative selection signals, TERT promoter mutations linked to age and smoking, smoking as promoter, FGFR3 negative selection, natural saturation mutagenesis, TP53 site selection, sex differences, and sampling design (dome
- transcript topics: Ultradeep duplex sequencing of normal urothelium; Driver mutations in RBM10, CDKN1A, ARID1A; Positive/negative selection signals (dN/dS, clustering, functional bias); TERT promoter activating mutations and association with age and smoking; Smoking as promoter rather than global mutagenesis; FGFR3 truncating mutations under negative selection

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 8
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- Ultradeep sequencing identified thousands of driver mutations across 16 genes in normal urothelium
- Men show higher truncating driver mutations in RBM10, CDKN1A, ARID1A than women
- Activating TERT promoter mutations detected in normal bladder tissue and associated with age and smoking
- TERT promoter mutations promote clonal expansions rather than globally increasing mutation density in smokers
- FGFR3 truncating mutations exhibit negative selection in normal urothelium
- Natural saturation mutagenesis observed in vivo via ultradeep sequencing, with TP53 site-specific positive selection

QC result: Pass.