Mutation Status in Circulating Tumor DNA from Patients with Metastatic Colorectal Cancer: Extended Mutation Analysis from the AGEO RASANC Study.
Fiche publication
Date publication
juillet 2019
Journal
Cancers
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BOUCHE Olivier, Dr VERNEREY Dewi, Mme MEURISSE Aurélia
Tous les auteurs :
Mas L, Bachet JB, Taly V, Bouché O, Taieb J, Cohen R, Meurisse A, Normand C, Gornet JM, Artru P, Louafi S, Thirot-Bidault A, Baumgaertner I, Coriat R, Tougeron D, Lecomte T, Mary F, Aparicio T, Marthey L, Blons H, Vernerey D, Laurent-Puig P
Lien Pubmed
Résumé
In patients with metastatic colorectal cancer (mCRC), and mutations are currently determined by tumor sample analysis. Here, we report mutation status analysis in paired tumor tissue and plasma samples of mCRC patients included in the AGEO RASANC prospective cohort study. Four hundred and twenty-five patients were enrolled. Plasma samples were analyzed by next-generation sequencing (NGS). When no mutation was identified, we used two methylated specific biomarkers (digital droplet PCR) to determine the presence or absence of circulating tumor DNA (ctDNA). Patients with conclusive ctDNA results were defined as those with at least one mutation or one methylated biomarker. The kappa coefficient and accuracy were 0.79 (95% CI: 0.67-0.91) and 97.3% (95% CI: 95.2-98.6%) between the status in plasma and tissue for patients with available paired samples ( = 405), and 0.89 (95% CI: 0.80-0.99) and 98.5% (95% CI: 96.4-99.5%) for those with conclusive ctDNA ( = 323). The absence of liver metastasis was the main factor associated to inconclusive ctDNA results. In patients with liver metastasis, the kappa coefficient was 0.91 (95% CI, 0.81-1.00) and accuracy was 98.6% (95% CI, 96.5-99.6%). We demonstrate satisfying concordance between tissue and plasma mutation detection, especially in patients with liver metastasis, arguing for plasma ctDNA testing for routine mutation analysis in these patients.
Mots clés
NGS, accuracy, circulating tumor DNA, colorectal cancer, liver metastases, methylated biomarker
Référence
Cancers (Basel). 2019 Jul 17;11(7):