Quantitative detection of EGFR mutations in circulating tumor DNA derived from lung adenocarcinomas
Menée sur 44 patients atteints d'un cancer du poumon, cette étude évalue l'intérêt d'analyser l'ADN tumoral circulant pour le suivi de la progression de la maladie au cours d'un traitement par inhibiteurs de l'activité tyrosine kinase d'EGFR
Purpose: Examination of somatic EGFR mutations is now a diagnostic routine for treatment of cancer using EGFR tyrosine kinase inhibitors (EGFR-TKI). Circulating tumor DNA (ctDNA) is a promising target for non-invasive diagnostics. We evaluated its utility by quantitatively detecting activating and resistant mutations, which were measured with BEAMing (beads, emulsion, amplification, and magnetics). Experimental Design: Twenty-three lung cancer patients with progressive disease after EGFR-TKI treatment and 21 patients who had never been treated with EGFR-TKIs were studied. Their primary tumors had activating mutations. In the plasma DNA of each patient, the activating mutation found in the corresponding primary tumor and the T790M resistance mutation were quantified by BEAMing. Results: In 32 out of 44 patients, activating mutations were detected in the plasma DNA (72.7%; 95% CI, 58.0 - 83.6%). The T790M mutation was detected in 10 out of 23 patients in the first group (43.5%; 95% CI, 25.6 - 53.4%). The ratio of T790M to activating mutations ranged from 13.3 to 94.0%. The peak of the distribution of the mutation allele fraction in the plasma DNA was in the 0.1 - 1% range. Conclusions: The major advantage of BEAMing is its ability to calculate the fraction of T790M-positive alleles from the alleles with activating mutations. This feature enables the detection of increases and decreases in the number of T790M mutations in cancer cells, regardless of normal cell DNA contamination, which may be useful for monitoring disease progression. ctDNA could potentially be used as an alternative method for EGFR mutation detection.
Clinical Cancer Research , résumé, 2011