Mutation and Expression Analysis of Gastrointestinal Stromal Tumor Associated Genes Spectrum in a Pakistani Male through Comprehensive Next-generation Sequencing

Abstract

Abstract Purpose This case study covers a Pakistani man with GIST at the gastroesophageal junction, which is rare and confirmed by CT scan and immunophenotyping (Desmin+, CD117+, SMA+) and we aimed to probe the mutational landscape through NGS techniques to elucidate the key genes mutations involved in incidence and progression of GIST.Methodology Mutational status is examined through whole exome sequencing and mRNA sequencing using tumor tissue against adjacent control tissue.Results These analyses revealed a number of deleterious mutations in genes associated with cancer, metabolism and RAS/RAF pathways. These include PDGFRA, NF1, SDHA, and others. The mRNA transcripts analysis revealed 2441 Differentially expressed genes (DEGs), among which 63 were upregulated and 137 were downregulated. These genes showed enrichment in biological processes such as cell adhesion matrix, metabolism, cellular senescence, and positive regulation of cellular component proliferation along with cancer-associated pathways such as PI3K/AKT, mTOR, and RAS. The common pathway results of the NGS analysis identified significantly deregulated genes including the upregulated GNB1 and CSFR3 while downregulated FOXD2, HES5, CDKN2C, FOXO6, TP73, RAP1GAP, RPS6KA1, PRKCZ, INNP5B. These genes showed enrichment in EMT, cell migration, and invasion by increased activation of the PI3K/AKT pathway.Conclusion NGS data analysis confirmed that these genes could play a key role in driving molecular pathways for gastrointestinal stromal tumorigenesis. This study provided a wide spectrum of molecular characterization of GISTs in Pakistani man and its first time reported and could be a pilot study for driver mutations and therapeutic aspects.