Clonal diversity in KRAS mutant colorectal adenocarcinoma under treatment: Monitoring of cfDNA using reverse hybridization and DNA sequencing platforms

Bádon, Emese Sarolta; Mokánszki, Attila; Mónus, Anikó; András, Csilla; Méhes, Gábor

doi:10.1016/j.mcp.2022.101891

Cited by 1 publication

(1 citation statement)

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“…In recent years, various studies have demonstrated the prognostic value of cfDNA in sCRC, raising the possibility that their analysis might identify patients with localized tumors who are at risk of recurrence [8]. Other studies have shown that molecular analysis of the tumor through liquid biopsies provides information about the changes in the RAS mutational status due to tumoral heterogeneity and selective pressure by targeted therapies throughout the course of the disease [9,10]. However, the significance of liquid biopsy in the clinical management of patients with synchronous metastases remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Circulating Tumor DNA in Synchronous Metastatic Colorectal Cancer at Diagnosis Predicts Overall Patient Survival

Sayagués,

Montero,

Jiménez-Pérez

et al. 2023

IJMS

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Sporadic colorectal cancer (sCRC) initially presents as metastatic tumors in 25–30% of patients. The 5-year overall survival (OS) in patients with metastatic sCRC is 50%, falling to 10% in patients presenting with synchronous metastatic disease (stage IV). In this study, we systematically analyzed the mutations of RAS, PIK3CA and BRAF genes in circulating tumor DNA (ctDNA) and tumoral tissue DNA (ttDNA) from 51 synchronous metastatic colorectal carcinoma (SMCC) patients by real-time PCR, and their relationship with the clinical, biological and histological features of disease at diagnosis. The highest frequency of mutations detected was in the KRAS gene, in tumor biopsies and plasma samples, followed by mutations of the PIK3CA, NRAS and BRAF genes. Overall, plasma systematically contained those genetic abnormalities observed in the tumor biopsy sample from the same subject, the largest discrepancies detected between the tumor biopsy and plasma from the same patient being for mutations in the KRAS and PIK3CA genes, with concordances of genotyping results between ttDNA and ctDNA at diagnosis of 75% and 84%, respectively. Of the 51 SMCC patients in the study, 25 (49%) showed mutations in at least 1 of the 4 genes analyzed in patient plasma. From the prognostic point of view, the presence and number of the most common mutations in the RAS, PIK3CA and BRAF genes in plasma from SMCC patients are independent prognostic factors for OS. Determination of the mutational status of ctDNA in SMCC could be a key tool for the clinical management of patients.

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Section: Discussionmentioning

confidence: 99%