Deciphering the Genetic Aberrations in DNA Damage Response Genes and Their Possible Association with HNSCC

Abstract

Head and neck squamous cell carcinoma (HNSCC) includes carcinomas in the oral cavity, pharynx and larynx. It is considered as the sixth most common form of cancer in the world. Several studies have confirmed that smoking and alcohol consumption are the major risk factors for HNSCC. DNA damage response genes play an important role in the maintenance of the genome. Defects in cell cycle checkpoint and DNA repair mechanisms, such as mutation or abnormalities, may lead to the wide spectrum of human diseases. The present study employs databases and computational tools to identify the genetic abnormalities associated with DNA damage related genes which might have a direct or indirect association with HNSCC. The demographic details of HNSCC patients was obtained from The Cancer Gene Atlas (TCGA, Firehose Legacy) dataset hosted by the cBioportal database. The oncoprint data analysis revealed the highest frequency of gene alteration in the ATR gene (15%), followed by ATM, BRCA2 and CHEK2 (5%). Other genes showed less than 5% alteration. The gene expression profile of ATR gene revealed its differential expression pattern in different grades of tumor relative to normal samples. The survival curve analysis using Kaplan-Meier method revealed that a high level expression of the ATR gene leads to poor survival rate in the female HNSCC patients when compared to males. Thus the present study has identified gross and single nucleotide variants in the ATR gene which could have a putative role in the development of tumor. Further experimental research is required to confirm this association.