Abstract 3698: A longitudinal investigation of temporal/intratumoral heterogeneity by plasma NGS profiling of mutation clones in metastatic colorectal cancer

Abstract Intratumoral tumor heterogeneity characterized by the presence of genetically and phenotypically distinct cell populations (clones) within the same lesion, represents a significant obstacle to accurate diagnosis, prognosis, and therapeutic targeting based on molecular investigation, when biopsy may yield incorrect results due to insufficient representation of all tumor clones in the sample. Liquid biopsy, defined as the detection and quantification of somatic aberrations of circulating tumor DNA (ctDNA) in blood plasma, has long been considered an approach that can be effectively applied to obtain full spectrum of mutations without any bias. This assumption based on condition that the release of ctDNA fragments occurs quantitatively from all present cell populations. Our study aims to verify this hypothesis based on continuous liquid biopsies in patients undergoing treatment for advanced solid tumors. In the field of liquid biopsy, the use of ctDNA detection for continuous monitoring of ongoing therapy has recently come to the forefront. The so-called "tumor informed" approach, in which somatic mutations found in tumor tissue are subsequently detected in ctDNA. The procedure is characterized by relatively low costs, which allows repeated examinations based on frequent sampling for continuous monitoring of the disease and treatment. In ctDNA-positive patients, we subsequently perform broad-spectrum longitudinal profiling of mutational clones in ctDNA using an NGS panel based on the principle of hybrid capture of a panel covering a total of 127 genes. This method is used to monitor mutation profiles in ctDNA from plasma of patients with metastatic colorectal cancer undergoing multimodal treatment including surgical resection of metastatic tissue and chemotherapy. The results indicate that the response to treatment, which is manifested by a decrease or increase in ctDNA represented by different mutations, may not occur homogeneously in all present mutational clones. In fact, some clonal populations appear to indicate earlier response than others, characterized by shifts in mutation fraction dynamics. Citation Format: Petra Kroupova, Barbora Minarikova, Andrea Chmelarova, Marek Minarik. A longitudinal investigation of temporal/intratumoral heterogeneity by plasma NGS profiling of mutation clones in metastatic colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3698.