Gene set enrichment analysis revealed potential pathways and gene networks underlying molecular mechanisms in overall lung cancer as well as histology subtypes development.
The results provide evidence that genetic interactions between oncogenesis-related genes play an important role in lung tumorigenesis and epistasis analysis, combined with functional annotation, provides a valuable tool for uncovering functional novel susceptibility genes that contribute to lung cancer development by interacting with other modifier genes.
Dr. Christopher I. Amos from the Biomedical Data Science Department at Dartmouth College in Hanover, NH, USA said, "Lung cancer, as one of the most common cancers worldwide, has a complex disease mechanism and both genetic and environmental factors, as well as the interactions among those factors contribute to development of this deadly disease"
Lung cancer, as one of the most common cancers worldwide, has a complex disease mechanism and both genetic and environmental factors, as well as the interactions among those factors contribute to the development of this deadly disease.
Neither of these two genes has been identified from main effect association analysis before, suggesting that genetic interactions, especially those among novel variants, remain unrevealed in lung cancer study.
An epistasis study among oncogenesis-related genes in lung cancer will help the authors identify oncogenes or tumor suppressors affecting early stages of lung cancer development that cannot be captured by single-locus analysis; provide insights about the connected pathways and genetic networks involved in lung cancer development; and discover novel targets for disease treatment.
Lung cancer is a heterogeneous disease and researchers have identified vast differences in genomic attributes, such as specific variants, gene mutation, gene expression and DNA methylation profile, etc., between adenocarcinoma and squamous cell carcinoma lung cancer subtype.
The availability of large lung cancer GWAS data from international collaboration enables the researchers to conduct a large-scale epistasis analysis among oncogenesis-related genes in overall lung cancer as well as lung cancer subtypes.
The Amos research team concluded, "We believe more genetic interactions including those with small effects and histology subtype-specific effects could be identified in the future as more samples with genotype data become available. With current knowledge, the information about the functional significance of the identified SNPs is remains limited our study, but we were fortunate to be able to analyze effects on joint genotypes from a study of lung tissues."
Full text - https://doi.org/10.18632/oncotarget.26678
Correspondence to - Christopher I. Amos - [email protected]
Keywords - lung adenocarcinoma, docetaxel, ABL kinases, differentiation, YAP1
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