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Multi-regional genomic and transcriptomic characterization of a melanoma-associated oral cavity cancer provide evidence for CASP8 alteration-mediated field cancerization.
Chakravarty, Shouvik; Ghosh, Arnab; Das, Chitrarpita; Das, Subrata; Patra, Subrata; Maitra, Arindam; Ghose, Sandip; Biswas, Nidhan K.
Afiliación
  • Chakravarty S; Biotechnology Research and Innovation Council, National Institute of Biomedical Genomics (BRIC-NIBMG), Kalyani, 741251, India.
  • Ghosh A; Biotechnology Research and Innovation Council-Regional Centre for Biotechnology (BRIC- RCB), Faridabad, India.
  • Das C; Biotechnology Research and Innovation Council, National Institute of Biomedical Genomics (BRIC-NIBMG), Kalyani, 741251, India.
  • Das S; Biotechnology Research and Innovation Council-Regional Centre for Biotechnology (BRIC- RCB), Faridabad, India.
  • Patra S; Biotechnology Research and Innovation Council, National Institute of Biomedical Genomics (BRIC-NIBMG), Kalyani, 741251, India.
  • Maitra A; Biotechnology Research and Innovation Council, National Institute of Biomedical Genomics (BRIC-NIBMG), Kalyani, 741251, India.
  • Ghose S; Biotechnology Research and Innovation Council, National Institute of Biomedical Genomics (BRIC-NIBMG), Kalyani, 741251, India.
  • Biswas NK; Biotechnology Research and Innovation Council, National Institute of Biomedical Genomics (BRIC-NIBMG), Kalyani, 741251, India.
Hum Genomics ; 18(1): 96, 2024 Sep 07.
Article en En | MEDLINE | ID: mdl-39244622
ABSTRACT

BACKGROUND:

Precancerous 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.

METHODS:

We 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.

RESULTS:

A 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.

CONCLUSION:

CASP8 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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Boca / Caspasa 8 / Variaciones en el Número de Copia de ADN / Transcriptoma / Melanoma Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Hum Genomics Asunto de la revista: GENETICA Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Boca / Caspasa 8 / Variaciones en el Número de Copia de ADN / Transcriptoma / Melanoma Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Hum Genomics Asunto de la revista: GENETICA Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido