Mutant DNA in plasma of lung cancer patients: potential for monitoring response to therapy
Abstract
The hypothesis tested was that mutant tumor DNA shed into plasma would show predictive value for monitoring response to therapy in non-small cell lung carcinoma patients. Pretreatment plasma specimens from 25 patients on a phase I trial were evaluated, 12 with paired posttreatment specimens, and 138 patients on the Southwest Oncology Group S0003 trial, 38 with paired posttreatment specimens, for the presence of K-RAS mutations. Thirteen tumor specimens from the phase I trial patients and seven tumor specimens from S0003 patients were also available for comparative analysis of K-RAS mutations in tumor tissue and plasma. All patients were treated similarly with paclitaxel, and carboplatin chemotherapy. DNA was extracted and mutational analyses performed using an RFLP-PCR assay. K-RAS mutations were found in plasma DNA in 5/25 of the phase I patients (20%). Median survival was 10 months in all patients, 11.4 months in the wild-type K-RAS group, and 3.3 months in the mutant K-RAS group (P = 0.056). Point mutations in plasma DNA were identical to mutations found in the tumors, confirming the tumor as the source. In two patients with K-RAS mutations pretreatment, posttreatment plasmas were evaluated: a patient with clinical progressi...Continue Reading
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Elimination of unaltered DNA in mixed clinical samples via nuclease-assisted minor-allele enrichment
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