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http://hdl.handle.net/123456789/28279
Title: | Mutational Landscape of Notch Pathway and its Mediators in Oral Squamous Cell Carcinoma through Whole Exome Sequencing |
Authors: | Sana Batool |
Keywords: | Biochemistry |
Issue Date: | 2023 |
Publisher: | Quaid I Azam university Islamabad |
Abstract: | Head and Neck cancer (HNC) is a broad term representing a group of tumors arising from mouth, throat, nasal cavity, and surrounding areas. The typical 5-year survival rate of such tumors is about 50% and is reported to be the 7th leading cancer worldwide. Among its commonest type, Oral Squamous Cell Carcinoma (OSCC) holds the 1st place, and it is the 2nd most predominant cancer in Pakistan. It starts when numerous mutations in oral squamous cells' DNA take place, giving the cells an illimitable capacity for proliferative growth. TP53, CDKN2A, NOTCH1, PTEN and CASP8 are frequently mutated driver genes of OSCC. This research sought to characterize OSCC samples molecularly to determine how Notch signaling contributes to the development of OSCC. To achieve this, Whole Exome Sequencing (WES) of three Tissue samples was compared with 3 control samples and In silico tools were applied to categorize the genetic mutations with a special focus on Notch Pathway. Careful research made us find a deletion in the PEST domain of NOTCH1, a non-synonymous substitution mutation in the linker region of HES1, in RING domain of DTX2 and domain A of CTBP2. Another deletion was observed in the TAD domain of MAML3 and an insertional mutation in the BTD domain of RBPJ gene. When all these mutations were analyzed through In silico software, RBPJ, NOTCH1 and MAML3 mutations were categorized as highly deleterious and disease causing. Overall, these mutations may contribute to OSCC by dysregulating the normal function of notch signaling. Additional transcriptome analysis and molecular docking can offer profound insights that might accelerate the creation of effective prognostic/diagnostic markers and aid in the development of new OSCC therapies. Keywords: Head and Neck Carcinoma (HNC), Oral Squamous Cell Carcinoma (OSCC), Whole Exome Sequencing (WES), Next generation Sequencing (NGS), Notch Pathway, Recombination Signal Binding Protein for Immunoglobulin Kappa J Region (RBPJ), Neurogenic locus notch homolog protein 1 (NOTCH1). |
URI: | http://hdl.handle.net/123456789/28279 |
Appears in Collections: | M.Phil |
Files in This Item:
File | Description | Size | Format | |
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BIO 7268.pdf | BIO 7268 | 2.42 MB | Adobe PDF | View/Open |
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