Abstract B016: Developing diagnostic tools via mutational spectra analysis and multiomic plasma profiling from liquid biopsies to identify potential signatures in cancer in Trinidad and Tobago

Abstract

Abstract Cancer, especially lung cancer is a leading cause of nosocomial deaths worldwide. Non-small cell lung cancer (NSCLC) has a five-year survival rate of only 24%. Early diagnoses markedly improves survival with personalized cancer therapies using non-invasive techniques for asymptomatic detection of mutational spectrum-related by genotyping NSCLC patients, even prior to symptoms. Analysis of conformational change in proteins due to mutations in oncogenes allow for mutation-specific treatment with specialized cancer drugs. In addition, tumor mutational burden (TMB) is a promising predictive biomarker for cancer immunotherapy as high TMB patients respond better to immune checkpoint inhibitors cancer drugs. Treatment planning for non-small cell lung cancer generally requires testing for EGFR, ALK, ROS1, BRAF, MET, RET and KRAS gene alterations or whole genome analysis to assess TMB. The Caribbean region remains disadvantaged by the lack of available genetic testing mainly due to accessibility. We propose the genotyping of 30 stage III-IV NSCLC patients via next-generation sequencing (NGS) to improve personalized therapies. Through the analysis of tumor-specific alterations amongst a complete mutation spectrum analysis, including single nucleotide variants (SNVs), insertions, deletions, copy number variations (CNVs), and methylation alterations, we would generate data to be used as an accurate form of cancer genotyping for diagnostic purposes. We intend to include these genes as biomarkers in a mutational spectrum analysis, to be collated into a predictive DNA assay to be used for the first time as a diagnostic/prognostic tool in a medically underserved community. We intend to also identify TMB-high patients without cost-prohibitive whole genome sequencing by focusing on DNA damage repair (DDR) genes. There is an increasing utilization of agnostic testing which involves the analysis of all potentially actionable genes across all tumor and cancer types. The invention of genomic-tailored specialized cancer treatments has resulted in a spectacular improvement in disease outcomes for a significant portion of cancer patients, which we hope to offer to improve clinical outcomes and prognosis in the racially diverse population of Trinidad and Tobago. Citation Format: Nicole Ramlachan, Samuel M. West. Developing diagnostic tools via mutational spectra analysis and multiomic plasma profiling from liquid biopsies to identify potential signatures in cancer in Trinidad and Tobago [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr B016.