Plasma mutation profile of precursor lesions and colorectal cancer using the Oncomine Colon cfDNA Assay.

Autor: Dos Reis MB; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil., Dos Santos W; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil., de Carvalho AC; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil., Lima AB; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil., Reis MT; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil.; Department of Pathology, Barretos Cancer Hospital, Barretos, SP, Brazil., Santos F; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil.; Department of Medical Oncology, Barretos Cancer Hospital, Barretos, SP, Brazil., Reis RM; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil. ruireis.hcb@gmail.com.; Life and Health Sciences Research Institute (ICVS), Medical School, University of Minho, Braga, Portugal. ruireis.hcb@gmail.com.; ICVS/3B's-PT Government Associate Laboratory, Braga, Portugal. ruireis.hcb@gmail.com., Guimarães DP; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil. guimaraes.dp@gmail.com.
Jazyk: angličtina
Zdroj: BMC cancer [BMC Cancer] 2024 Dec 18; Vol. 24 (1), pp. 1547. Date of Electronic Publication: 2024 Dec 18.
DOI: 10.1186/s12885-024-13287-2
Abstrakt: Background: Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Early detection of precursor lesions or early-stage cancer could hamper cancer development or improve survival rates. Liquid biopsy, which detects tumor biomarkers, such as mutations, in blood, is a promising avenue for cancer screening.
Aim: To assess the presence of genetic variants in plasma cell-free tumor DNA from patients with precursor lesions and colorectal cancer using the commercial Oncomine Colon cfDNA Assay.
Material and Methods: Cell-free DNA (cfDNA) samples from the plasma of 52 Brazilian patients were analyzed. Eight patients did not have any significant lesions (five normal colonoscopies and three hyperplastic polyps), 24 exhibited precursor lesions (13 nonadvanced adenomas, 10 advanced adenomas, and one sessile serrated lesion), and 20 patients with cancer (CRC). The mutation profile of 14 CRC-associated genes were determined by next-generation sequencing (NGS) using the Oncomine Colon cfDNA Assay in the Ion Torrent PGM/S5 sequencer.
Results: Thirty-three variants were detected in eight genes (TP53, PIK3CA, FBXW7, APC, BRAF, GNAS, KRAS, and SMAD4). No variants were detected in the AKT1, CTNNB1, EGFR, ERBB2, MAP2K1 and NRAS genes. All variants were considered pathogenic and classified as missense or truncating. The TP53 gene harbored the most variants (48.48%), followed by the KRAS gene (15.15%) and the APC gene (9.09%). It was possible to detect the presence of at least one pathogenic variant in cfDNA in 60% of CRC patients (12/20) and 25% of precursor lesions (6/24), which included variants in three patients with nonadvanced adenoma (3/13 - 23.08%) and three with advanced adenomas (3/10 - 30%). No variants were detected in the eight patients with normal findings during colonoscopy. The detection of mutations showed a sensitivity of 60% and a specificity of 100% for detecting CRC and a sensitivity of 50% and a specificity of 100% for detecting advanced lesions.
Conclusion: The detection of plasma NGS-identified mutations could assist in early screening and diagnostic of CRC in a noninvasive manner.
Competing Interests: Declarations. Ethics approval and consent to participate: The Research Institutional Board of the Barretos Cancer Hospital approved the study (753/2013 and 1060/2015), and all patients signed informed consent before enrollment. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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