ArticleBritish journal of cancer2022
Clonal relationship and alcohol consumption-associated mutational signature in synchronous hypopharyngeal tumours and oesophageal squamous cell carcinoma.
Article in British journal of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- Effects of ethanol and acetaldehyde on multi-organ genomic mutation landscapes.Cell biology and toxicology · 2026Article
- Mutational signature-based classification uncovers emerging oral cancer subtypes with distinct molecular patterns.International journal of oral science · 2026Article
- Esophageal cancer: from pathogenesis to precision therapies.Signal transduction and targeted therapy · 2026Review
- Dual pancreatic carcinomas: clonally related or independent primaries?NPJ precision oncology · 2026Article
- Analysis of the associations between DNA methylation and clinical features reveals the potential oncogenic effect of CFAP52 in esophageal squamous cell cancer.Cancer cell international · 2025Article
- Oncogenic NFE2L2 mutations in plasma ctDNA and tumors are predictors and prognosticators of chemoradiation therapy in resectable esophageal squamous cell carcinoma.British journal of cancer · 2025Article
- Genome-scale multi-organ analysis of mutagenic effects of ethanol and acetaldehyde in Sprague Dawley rats.bioRxiv : the preprint server for biology · 2025Article
- Ethanol induces replication fork stalling and membrane stress in immortalized laryngeal cells.iScience · 2023Article
- Elucidating the clonal relationship of esophageal second primary tumors in patients with laryngeal squamous cell carcinoma.Infectious agents and cancer · 2023Review
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Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe patients with dual oesophageal squamous cell carcinoma (ESCC) and hypopharyngeal cancer (HPC) have poor prognosis; their underlying genetic pathogenesis is unclear. We hypothesise that development of synchronous ESCC/HPC depends on multicentricity or independent origin, rather than multifocality due to local or lateral spreading.
methodMultiple region whole-exome sequencing (M-WES) and clonality analysis were used to assess clonal relationship and spatial inter- or intra-tumour heterogeneity (ITH) in 62 tumour regions from eight dual ESCC/HPC and ten ESCC patients.
resultsAll synchronous ESCC/HPC patients had COSMIC 16 mutation signatures, compared to only 40% ESCC in the current study (p = 0.013) and public data set (n = 165, p = 0.003). This alcohol consumption-related mutation signature 16, commonly involved in multiple alcohol-related cancers, was significantly associated with drinking and alcohol metabolism-related ADH1B rs1229984. The mutational landscape and copy number profiles were completely distinct between the two primary tumours; clonality analysis further suggested the two primary tumours shared no or only one clone accompanying independent subclone evolution. M-WES strategy demonstrated higher sensitivity and accuracy for detection of mutational prevalence and the late branch mutations among different regions in the ESCC tumours, compared to traditional sequencing analysis based on single biopsy strategy. Patients with high ITH assessed by cancer cell fraction analysis after M-WES were significantly associated with both relapse and survival.
conclusionsOur hypothesis-generating M-WES ITH assessment data have implications for prognostication. Collectively, our findings support multicentric independent clonal evolution, the field cancerisation theory, and suggest novel insights implicating an aetiologic role of alcohol metabolism in dual ESCC/HPC carcinogenesis.
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