Clinical relevance of KRAS-mutated sub-clones detected with picodroplet digital PCR in advanced colorectal cancer treated with anti-EGFR therapy.
Fiche publication
Date publication
septembre 2014
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BOUCHE Olivier
Tous les auteurs :
Laurent-Puig P, Pekin D, Normand C, K Kotsopoulos S, Nizard P, Perez Toralla K, Rowell R, Olson J, Srinivasan P, Le Corre D, Hor T, El Harrak Z, Li X, Link D, Bouche O, Emile JF, Landi B, Boige V, Hutchison B, Taly V
Lien Pubmed
Résumé
Purpose: KRAS mutations are predictive of non-response to anti-EGFR therapies in metastatic colorectal cancer (mCRC). However, only 50% of non-mutated patients benefit from them. KRAS-mutated subclonal populations non-detectable by conventional methods have been suggested as the cause of early progression. Molecular analysis technology with high sensitivity and precision are required to test this hypothesis. Experimental design: From 2 cohorts of mCRC patients, 136 KRAS, NRAS and BRAF wild-type tumors with sufficient tumor materiel to perform highly-sensitive picodroplet digital PCR (dPCR) and 41 KRAS-mutated tumor were selected. All these patients were treated by anti-EGFR therapy. dPCR was used for KRAS or BRAF mutations screening and compared to quantitative PCR (qPCR). Progression free survival (PFS) and overall survival (OS) were analyzed according to the KRAS-mutated allele fraction. Results: In addition to the confirmation of the 41 patients with KRAS-mutated tumors, dPCR also identified KRAS mutations in 22 samples considered as KRAS wild-type by qPCR. The fraction of KRAS-mutated allele quantified by dPCR was inversely correlated with anti-EGFR therapy response rate (P
Référence
Clin Cancer Res. 2014 Sep 23. pii: clincanres.0983.2014.