Dataset Information

Decoding the Genetic Alterations in Genes of DNMT Family (DNA Methyl-Transferase) and their Association with Head and Neck Squamous Cell Carcinoma.

ABSTRACT:

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.
.

SUBMITTER: Fathima T

PROVIDER: S-EPMC8046301 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Head and neck squamous cell carcinoma (HNSCC) arises from the epithelial lining of the oral cavity, hypopharynx, oropharynx, and larynx. There are several potential risk factors that cause the generation of HNSCC, including cigarette smoking, alcohol consumption, betel quid chewing, inadequate nutrition, poor oral hygiene, HPV and Epstein-Barr virus, and Candida albicans infections. HNSCC has causative links to both environmental factors and genetic mutations, with the latter playing a more critical role in cancer progression. These molecular changes to epithelial cells include the inactivation of cancer suppressor genes and proto-oncogenes overexpression, resulting in tumour cell proliferation and distant metastasis. HNSCC patients have impaired dendritic cell (DC) and natural killer (NK) cell functions, increased production of higher immune-suppressive molecules, loss of regulatory T cells and co-stimulatory molecules and major histocompatibility complex (MHC) class Ι molecules, lower number of lymphocyte subsets, and a poor response to antigen-presenting cells. At present, the standard treatment modalities for HNSCC patients include surgery, chemotherapy and radiotherapy, and combinatorial therapy. Despite advances in the development of novel treatment modalities over the last few decades, survival rates of HNSCC patients have not increased. To establish effective immunotherapies, a greater understanding of interactions between the immune system and HNSCC is required, and there is a particular need to develop novel therapeutic options. A therapeutic cancer vaccine has been proposed as a promising method to improve outcome by inducing a powerful adaptive immune response that leads to cancer cell elimination. Compared with other vaccines, peptide cancer vaccines are more robust and specific. In the past few years, there have been remarkable achievements in peptide-based vaccines for HNSCC patients. Here, we summarize the latest molecular alterations in HNSCC, explore the immune response to HNSCC, and discuss the latest developments in peptide-based cancer vaccine strategies. This review highlights areas for valuable future research focusing on peptide-based cancer vaccines.