ArticleNature communications2025
APOBEC affects tumor evolution and age at onset of lung cancer in smokers.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Genomic instability, postoperative recurrence and therapeutic vulnerabilities in resectable non‑small cell lung cancer (Review).Oncology reports · 2026Review
- Motif-centered analyses reveal universal and tissue-specific mutagenic mechanisms operating in the human body.NAR cancer · 2026Article
- Shared Transcriptomic Signatures and Network Interactions Between Lung Adenocarcinoma and Asthma.International journal of molecular sciences · 2026Article
- Motif-Centered Analyses Reveal Universal and Tissue-Specific Mutagenic Mechanisms Operating in the Human Body.bioRxiv : the preprint server for biology · 2026Article
- Single base focal hypermutation cooccurs with structural variation as an early event in advanced prostate tumourigenesis with ancestry specific independence: a multi-ancestral observational study.Genome medicine · 2026Observational
- A Prognostic Signature for Lung Adenocarcinoma in Patients Who Have Never Smoked.Cancer discovery · 2026Article
- High-dimensional partial linear model with trend filtering.Electronic journal of statistics · 2026Article
- APOBEC3A-Induced DNA Damage Drives Polymerase θ Dependency and Synthetic Lethality in Cancer.bioRxiv : the preprint server for biology · 2025Article
- Panorama of Chromosomal Instability in Lung Cancer.medRxiv : the preprint server for health sciences · 2025Article
- A prognostic signature for lung adenocarcinoma in people who have never smoked.bioRxiv : the preprint server for biology · 2025Article
- Article
- A Thiopurine-like Mutagenic Process Defines TGCT Subtypes.bioRxiv : the preprint server for biology · 2025Article
- Tobacco smoke carcinogens exacerbate APOBEC mutagenesis and carcinogenesis.Research square · 2025Article
- Tobacco smoke carcinogens exacerbate APOBEC mutagenesis and carcinogenesis.bioRxiv : the preprint server for biology · 2025Article
- The mutagenic forces shaping the genomic landscape of lung cancer in never smokers.medRxiv : the preprint server for health sciences · 2024Article
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Authors and funding
31 authors.
Funding
Abstract
Most solid tumors harbor somatic mutations attributed to off-target activities of APOBEC3A (A3A) and/or APOBEC3B (A3B). However, how APOBEC3A/B enzymes affect tumor evolution in the presence of exogenous mutagenic processes is largely unknown. Here, multi-omics profiling of 309 lung cancers from smokers identifies two subtypes defined by low (LAS) and high (HAS) APOBEC mutagenesis. LAS are enriched for A3B-like mutagenesis and KRAS mutations; HAS for A3A-like mutagenesis and TP53 mutations. Compared to LAS, HAS have older age at onset and high proportions of newly generated progenitor-like cells likely due to the combined tobacco smoking- and APOBEC3A-associated DNA damage and apoptosis. Consistently, HAS exhibit high expression of pulmonary healing signaling pathway, stemness markers, distal cell-of-origin, more neoantigens, slower clonal expansion, but no smoking-associated genomic/epigenomic changes. With validation in 184 lung tumor samples, these findings show how heterogeneity in mutational burden across co-occurring mutational processes and cell types contributes to tumor development.
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