Whole exome sequencing identifies somatically mutated genes in bladder cancer: A pilot study from Bangladesh

Bladder cancer, ranking as the tenth most common cancer globally, lacks genomic characterization in Bangladeshi patients. This study is an exploratory analysis of the genomic landscape of bladder cancer in this population by conducting whole-exome sequencing (WES) on tumor (median coverage = 65X) and matched blood (median coverage = 68X) samples from four patients at the National Institute of Cancer Research and Hospital in Dhaka, using the Illumina HiSeq platform. Somatic mutations were identified using GATK Mutect2 and analyzed with bioinformatics tools to explore potential genetic alterations in those four individuals. Single Nucleotide Variants (SNVs) were observed in TP53 (25%, 1/4), KMT2C (75%, 3/4), and FLG (100%, 4/4), with mutations in AHNAK2 (75%, 3/4) and KCNJ18 (50%, 2/4) in this limited cohort. Pathway analysis highlighted possible disruptions in RTK-RAS and NOTCH signaling pathways, which are critical for cell proliferation and differentiation. Mutational signature analysis from the four sample data revealed the single base substitution (SBS2) signature, which is linked to APOBEC activity and SBS3 linked to defects in homologous recombination based DNA repair. Additionally, copy number variations (CNVs) were evaluated, identifying chromosomal losses (e.g., Y chromosome, 1p12, 9p21.2-p21.3) and gains (e.g., 1q21.3, 6p22.3). This study establishes a foundational dataset for Bangladeshi bladder cancer patients, paving the way for further validation experiments in vitro, and the possibility of developing population-specific molecular biomarker panels, these insights may also contribute to personalized treatment strategies and help combat rising morbidity and recurrence rates of bladder cancer in Bangladesh.