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AuthorKumar S, Udhaya
AuthorBalasundaram, Ambritha
AuthorCathryn R, Hephzibah
AuthorVarghese, Rinku Polachirakkal
AuthorR, Siva
AuthorR, Gnanasambandan
AuthorYounes, Salma
AuthorZayed, Hatem
AuthorDoss C, George Priya
Available date2022-12-15T08:24:44Z
Publication Date2022
Publication NameComputers in Biology and Medicine
ResourceScopus
URIhttp://dx.doi.org/10.1016/j.compbiomed.2022.105701
URIhttp://hdl.handle.net/10576/37346
AbstractBackground: Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer. NSCLC accounts for 84% of all lung cancer cases. In recent years, advances in pathway understanding, methods for discovering novel genetic biomarkers, and new drugs designed to inhibit the signaling cascades have enabled clinicians to personalize therapy for NSCLC. Objectives: The primary aim of this study is to identify the genes associated with NSCLC that harbor pathogenic variants that could be causative for NSCLC. The second aim is to investigate their roles in different pathways that lead to NSCLC. Methods: We examined exome-sequencing datasets from 54 NSCLC patients to characterize the variants associated with NSCLC. Results: Our findings revealed that 17 variants in 14 genes were considered highly pathogenic, including CDKN2A, ERBB2, FOXP1, IDH1, JAK3, KMT2D, K-Ras, MSH3, MSH6, POLE, RNF43, TCF7L2, TP53, and TSC1. Gene set enrichment analysis revealed the involvement of transmembrane receptor protein tyrosine kinase activity, protein binding, ATP binding, phosphatidylinositol-4,5-bisphosphate 3-kinase, and Ras guanyl-nucleotide exchange factor activity. Pathway analysis of these genes yielded different cancer-related pathways, including colorectal, prostate, endometrial, pancreatic, PI3K-Akt signaling pathways, and signaling pathways regulating pluripotency of stem cells. Module 1 from protein-protein interactions (PPIs) identified genes that harbor pathogenic SNPs. Three of the most deleterious SNPs are ERBB2 (rs1196929947), K-Ras (rs121913529), and POLE (rs751425952). Interestingly, one patient has a pathogenic K-Ras variant (rs121913529) co-occurred with the missense variant (rs752054698) inTSC1 gene. Conclusion: This study maps highly pathogenic variants associated with NSCLC and investigates their contributions to the pathogenesis of NSCLC. This study sheds light on the potential applications of precision medicine in patients with NSCLC. 2022 Elsevier Ltd
SponsorThe authors would like to take this opportunity to thank the management of Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India, and Qatar University, Doha, Qatar, for providing the necessary facilities and encouragement to carry out this work.
Languageen
PublisherElsevier
SubjectNon-small cell lung cancer
Non-synonymous single nucleotide polymorphisms
Pathogenic variants
Pathway enrichment analysis
PPI network
Precision medicine
Whole-exome sequencing
TitleWhole-exome sequencing analysis of NSCLC reveals the pathogenic missense variants from cancer-associated genes
TypeArticle
Volume Number148
dc.accessType Abstract Only


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