ArticleHuman genomics2024
Multi-regional genomic and transcriptomic characterization of a melanoma-associated oral cavity cancer provide evidence for CASP8 alteration-mediated field cancerization.
Article in Human genomics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Trends in Head and Neck Cancer: Oral Cavity Carcinoma and What the Radiologist Needs to Know.Radiology. Imaging cancer · 2025Review
- Review
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8 authors.
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Abstract
backgroundPrecancerous and malignant tumours arise within the oral cavity from a predisposed "field" of epithelial cells upon exposure to carcinogenic stimulus. This phenomenon is known as "Field Cancerization". The molecular genomic and transcriptomic alterations that lead to field cancerization and tumour progression is unknown in Indian Oral squamous cell carcinoma (OSCC) patients.
methodsWe have performed whole exome sequencing, copy-number variation array and whole transcriptome sequencing from five tumours and dysplastic lesions (sampled from distinct anatomical subsites - one each from buccal anterior and posterior alveolus, dorsum of tongue-mucosal melanoma, lip and left buccal mucosa) and blood from a rare OSCC patient with field cancerization.
resultsA missense CASP8 gene mutation (p.S375F) was observed to be the initiating event in oral tumour field development. APOBEC mutation signatures, arm-level copy number alterations, depletion of CD8 + T cells and activated NK cells and enrichment of pro-inflammatory mast cells were features of early-originating tumours. Pharmacological inhibition of CASP8 protein in a CASP8-wild type OSCC cell line showed enhanced levels of cellular migration and viability.
conclusionCASP8 alterations are the earliest driving events in oral field carcinogenesis, whereas additional somatic mutational, copy number and transcriptomic alterations ultimately lead to OSCC tumour formation and progression.
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