Characterization of molecular heterogeneity of colorectal cancer among Bangladeshi population by targeted next generation sequencing

Background Since the Sanger sequencing procedure was invented, scientists all over the world have been working to improve and further develop this cutting-edge technology. Next-generation sequencing (NGS) is a game-changing advancement and the ability to profile genetic changes in cancer in great detail has been made possible by recent advances in sequencing technology. Several studies produced high-quality data in terms of mutation identification, particularly in the areas of actionable or rarely mutated genes, epigenetics, and transcriptomics. The goal of this project is to look at genetic heterogeneity in Bangladeshi colorectal cancer patients so that cost-effective precision medicine can be developed applied in Bangladesh. Methods The mutational characteristics of 24 colorectal tumor samples from Bangladeshi patients were investigated using targeted next generation sequencing to explore the association of mutations with clinical aspects. A total of 50 genes were sequenced with an average target depth of 675X. Results The left-sided tumors had higher mutation frequencies in TP53, APC, and ATM, while the right-sided tumors had higher mutation frequencies in EZH2, HNF1A, HRAS, and PIK3CA. Almost all of the samples in this study had a mutation in FGFR3. Deleterious mutations in the APC gene (94%) provided a selective advantage to the nascent intestinal tumor cell via constitutional stimulation of the Wnt signal transduction pathway and chromosomal instability. CDKN2A nonsynonymous mutations were found in almost all patient samples, with the exception of one. In a different patient with three unique mutations, 17 samples (71%) had a mutation in SMAD4 located in exon5 (p.P223N) synonymous and nonsynonymous mutations (two in NGRI04, and one in NGRI10). Several genes, including ATM, CDH1, ERBB4, and FBXW7, have been identified as being significantly affected by TNM stages. Except for a few key colorectal cancer genes, a comparison of mutational characteristics with subjects from other countries’ independent data re vealed that the identified mutational characteristics are largely Bangladesh-specific. Conclusion In Bangladesh, precision medicine development and use in colorectal cancer are poorly addressed. The pilot study will serve as a starting point for genomics research into colon cancer in poor-resource settings like Bangladesh. The relationship between metastasis and genomic markers will aid in the identification of prospective intervention markers and the development of therapeutic options at the individual level, resulting in the development of precision medicine. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Social Science and Research Council, Ministry of Planning, Bangladesh ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All relevant ethical guidelines have been followed, and the study was approved by North South University IRB / ethics committee approvals have been obtained. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Datasets will be available upon request