SEMINAR
"Genomic Alterations of Mitochondrial DNA in Gingivobuccal Oral Squamous Cell Carcinoma: Extranuclear Clues in Disease Progress"


By
Dr. Arindam Maitra
Scientist, NIBMG, Kalyani


On
28th May 2019
11:55 AM


At
CDFD Seminar Hall,
3rd floor
Uppal

ABSTRACT :


Mitochondrial alterations are known to be involved in the process of tumorigenesis. Oral squamous cell carcinoma of the gingivobuccal region (OSCCGB) is the most prevalent form of cancer among males in the Indian subcontinent. Here we have investigated the impact of pathogenic mitochondrial mutations on disease severity in oral cancer patients. In addition to genetic and transcriptomic level correlation, we have also investigated nuclear mitochondrial inserts (numts) as a form of physical level mito-nuclear interaction in OSCC-GB patients.

We have found evidence of positive selection of somatic nonsynonymous mutations. Non-synonymous mutations in mitochondrial respiratory genes were found to increase the risk of lymph node metastasis. We have observed a significant reduction in mitochondrial DNA copy number in tumor DNA of these patients compared to the DNA from adjacent normal tissue samples. Analysis of transcriptome data of tumor and adjacent normal tissue revealed patients harboring mutations in mitochondrial protein-coding genes exhibited reduced expression of mitochondrial transcripts.

Mitochondrial non-synonymous somatic mutations might play driver role in OSCC-GB. This observation is further reinforced by the higher occurrence of LNM in patients carrying nonsynonymous somatic mutations over the patients carrying no such mutations. In presence of intact TP53, mtDNA somatic mutations and other driver mutations might aid in tumorigenesis interactively. We did not find any evidence of implication of Numts in gingivobuccal oral squamous cell carcinoma.