Dados do Trabalho

Título

PLASMA CELL-FREE TUMOR DNA DETECTION OF PATHOGENIC VARIANTS IN PATIENTS WITH PRECURSOR LESIONS AND COLORECTAL CANCER

Introdução

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 inner wall of 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 is essential for reducing the mortality rate. In this context, the early detection of tumors based on blood markers could provide benefits for improving the survival rate of CRC patients and has emerged as a promising avenue for cancer screening.

Objetivo

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.

Método

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.

Resultado

Forty-seven variants were detected in nine genes (TP53, PIK3CA, FBXW7, APC, BRAF, GNAS, KRAS, MAP2K1, and SMAD4). All variants were classified as missense or truncating and considered as pathogenic. 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 fourteen CRC (14/28 - 50%) and 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%). 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).

Conclusão

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

Palavras-chave

Colorectal cancer, liquid biopsy, screening