Rebiopsy of Lung Cancer Patients with Acquired Resistance to EGFR Inhibitors and Enhanced Detection of the T790M Mutation Using a Locked Nucleic Acid-Based Assay

摘要: Background: The epidermal growth factor receptor ( EGFR ) mutation T790M is reported in approximately 50% of lung cancers with acquired resistance to inhibitors and a potential prognostic predictive biomarker. Its assessment can be challenging due limited tissue availability underdetection at low mutant allele levels. Here, we sought determine the feasibility tumor rebiopsy more accurately assess prevalence using highly sensitive locked nucleic acid (LNA) PCR/sequencing assay. MET amplification was also analyzed. Methods: Patients were rebiopsied samples studied for sensitizing mutations. Positive cases evaluated standard PCR-based methods subset re-evaluated an LNA-PCR/sequencing method analytical sensitivity 0.1%. assessed by FISH. Results: Of 121 patients undergoing sampling, 104 (86%) successfully analyzed Most failures related content. All (61/61) matched pretreatment specimens showed concordance original mutation. Standard analysis on 99 detected 51(51%) mutants. Retesting 30 negative LNA-based 11 additional mutants estimated 68%. amplified 11% (4/37). Conclusions: re-biopsy cancer feasible provides sufficient material most patients. Using high methods, up 68% these Clin Cancer Res; 17(5); 1169–80. ©2011 AACR .