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bioRxiv · 10.1101/2024.11.16.623931

Combined analysis of somatic mutations and gene expression reveals nuclear speckles-associated enhanced stemness in gingivobuccal carcinoma under DNA damage response

Kumar, S.·De, T.·Subramani, J.·Rangarajan, A.·Pal, D.
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Abstract

Smokeless tobacco chewing habits in India lead to a high prevalence of Gingivobuccal oral squamous cell carcinoma (OSCC-GB). Cancer stem cells (CSCs) are a sub-population of cancer cells within a tumor with stem-like properties and are believed to contribute to tumor initiation, progression, increased resistance to drug therapy, and promote post-therapeutic cancer relapse. An RNA-seq data-based integrative analysis of somatic mutation and gene expression was performed to explore the role of CSCs in disease progression using the novel Indian-origin OSCC-GB cell line IIOC019 from a patient with tobacco-chewing habit. The identified DNA damage-related known mutational signature (ID1, SBS5) indicates the impact of smokeless tobacco-related carcinogens in the IIOC019 cell line. The differentially expressed somatic variants, functional impact predictions, and survival analysis reveal the role of DNA damage response (DDR)-related genes in OSCC-GB, with the SON gene as a significant player. The study suggests that the loss of function in a somatic variant of the SON gene is associated with enhanced stemness and increased risk of disease progression in OSCC-GB under DDR conditions. The newly identified CSC-associated somatic variants appear to promote cancer spread, local recurrence, and resistance to chemotherapy or radiotherapy, contributing to the high mortality rates among Indian OSCC-GB patients.

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Kumar, S., De, T., Subramani, J., Rangarajan, A., Pal, D.. 2024-11-18. Combined analysis of somatic mutations and gene expression reveals nuclear speckles-associated enhanced stemness in gingivobuccal carcinoma under DNA damage response. https://doi.org/10.1101/2024.11.16.623931

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