Abstract 3380: Use of liquid biopsy for detection of pathogenic variants in cell-free tumor DNA from patients with precursor lesions and colorectal cancer
Authors: Reis Mariana Bisarro Dos , Santos Wellington dos , de Carvalho Ana Carolina , Brandão Adhara , Brandão Adhara , Matsushita Marcus , Reis Rui Manuel , Guimarães Denise Peixoto 
Published: April 2023

Background: Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. The development of colorectal cancer is composed of multiple stages, starting with benign polyps in the large intestine and rectum, and gradually progress to carcinomas, providing a window of opportunity for early detection. Early diagnosis increases the survival rate of patients, thus making screening tests for precursor lesions (PL) and early-stage CRC essential for reducing the mortality rate. In this context, the early detection of tumors based on liquid biopsy could provide benefits for improving the survival rate of CRC patients and has emerged as a promising avenue for cancer screening. The aim of the study was to evaluate the presence of variants in plasma cell-free tumor DNA from patients with PL and CCR to identify diagnostic and early screening biomarkers.

Material and Methods: The cell-free DNA (cfDNA) samples were obtained from plasma of patients that underwent diagnostic colonoscopy. Eight patients did not have any significant lesions (normal colonoscopy or hyperplastic polyp) and were classified as normal (N), 28 as CRC and 23 as PL - 13 as early adenomas (EA), 9 advanced adenomas (AA), and 1 sessile serrated lesion (SSL). In addition, the genomic DNA samples from 2 FFPE tumor matched pair samples were analyzed. Analysis of variants in 14 CRC associated genes was performed using Oncomine Colon cfDNA Assay and Ion Torrent PGM/S5 sequencer.

Results and discussion: All variants were classified as missense or truncating and considered as pathogenic. Forty-seven variants were detected in nine genes (TP53, PIK3CA,FBXW7, APC, BRAF, GNAS, KRAS, MAP2K1, and SMAD4). TP53 gene showed the highest number of variants, comprising 53.19% of all detected variants, followed by KRAS (10.63%) and APC (8.51%). It was possible to detect the presence of at least one variant in ctDNA for 5 PL (5/23 - 21.73%) patients, including variants in 3 patients with early adenoma (3/13 - 23.07%) and 2 with advanced adenomas (2/9 - 22.22%) and fourteen CRC (14/28 - 50%). No variants were detected in patients with normal findings during colonoscopy. Concordance between detected variants in tumor tissue and plasma ctDNA (from matched samples) was observed only for two variants for CRC patients (GNAS and KRAS).

Conclusion: The detection of variants in liquid biopsy demonstrates the potential for non-invasive early screening and diagnostic of CRC.

Citation Format: Mariana Bisarro Dos Reis, Wellington dos Santos, Ana Carolina de Carvalho, Adhara Brandão, Adhara Brandão, Marcus Matsushita, Rui Manuel Reis, Denise Peixoto Guimarães. Use of liquid biopsy for detection of pathogenic variants in cell-free tumor DNA from patients with precursor lesions and colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3380.