Deep sequencing reveals recurrent somatic mutations and distinct molecular subgroups in gastric cancer in Mizo population, North East India

• Published in: Genomics (San Diego, Calif.) Calif.), 2023-11, Vol.115 (6), p.110741, Article 110741
• Main Authors: Chakraborty, Payel, Kurkalang, Sillarine, Ghatak, Souvik, Das, Subrata, Palodhi, Arindam, Sarkar, Sumanta, Dhar, Ranjan, Chenkual, Saia, Pachuau, Lalawmpuii, Zohmingthanga, John, Pautu, Jeremy L, Zomuana, Thomas, Lalruatfela, Sailo Tlau, Zothanzama, John, Kumar, Nachimuthu Senthil, Maitra, Arindam
• Format: Article
• Language: English
• ISSN: 0888-7543; 1089-8646; 1089-8646
• DOI: 10.1016/j.ygeno.2023.110741

In India, Mizoram has the highest incidence of gastric cancer (GC) which might be associated with environmental factors such as diet, Helicobacter pylori (H.pylori) and Epstein-Barr virus (EBV) infections, and somatic genomic alterations. We performed PCR cum sequencing and fragment analysis for detection of H. pylori/EBV infection and microsatellite Instability (MSI) in GC patients (N = 68). Somatic mutations were identified by targeted and exome sequencing. We found 87% of GC patients infected with H. pylori and or EBV. Pathogenic infections were mostly mutually exclusive with only 16% of coinfection. TP53, MUC6, and ARID1A were significantly mutated. Two molecular subgroups with distinctive mutational profiles were identified: (1) patients harboring mutations in TP53 and (2) patients harboring mutations in RTK/RAS/PI3-K signaling pathway and chromatin-remodeling genes. Therefore, EBV and H. pylori infections and somatic mutations in the genes involved in RTK/RAS/PI3K signaling pathway, chromatin-remodeling, and TP53 might drive GC development and progression in Mizo patients.