Objective: Epigenetic modifications are gaining focus due to their indirect association with tumorigenesis. DNA methylation plays a prime role in regulation of gene expression. Any aberrations in this gene family may lead to chromosomal instability and increased magnitude of tumour progression. In line with the above fact, the present study has been designed to identify genetic alterations in the genes of the DNMT (DNA methyl-transferase) family among head and neck squamous cell carcinoma patients (HNSCC).
Methods: The present study follows an observational design employing computational tools for analysis. The TCGA-Firehose Legacy data was assessed using the cBioportal database. The dataset comprised of 530 samples from HNSCC patients which were assessed for genetic alterations in the DNMT family. Furthermore, the protein stability analysis and pathogenicity of the mutations were assessed using I-Mutant Suite and PROVEAN tools.
Results: Almost all genes of the DNMT family harboured gene amplification. The TRDMT1 and DNMT3L genes showed deep deletions. Apart from these several non-synonymous, truncating and splice-site mutations were also documented. Protein stability and pathogenicity analysis revealed that majority of the mutations were found to decrease the stability and impose pathogenicity. Upon probing for reported mutations using gnomAD database, around six reference single nucleotide polymorphisms were identified which were found to exhibit a minor allele frequency less than 0.01.
Conclusions: Screening of an exhaustive collection of patient's samples could provide immense knowledge about the disease pathogenesis and identification of therapeutic leads. The variants identified in the present study could be used as diagnostic markers. However, further experimental analysis through genotyping assay is warranted to validate the present findings.<br />.
Keywords: HNSCC; In Silico; methyltransferases; mutations.