EGFR T790M mutation occurs in half of non-small cell lung cancer (NSCLC) patients with acquired EGFR-TKI (TKI) resistance, based on tumor re-biopsies using an invasive clinical procedure. Here, we dynamically monitored T790M mutation in circulating tumor DNA (ctDNA) using serial plasma samples from NSCLC patients receiving TKI through Droplet Digital PCR (ddPCR) method and the associations between overall survival (OS) starting from initial TKI treatment and the T790M ctDNA status detected in plasma were analyzed. Among 318 patients, 117 who acquired TKI resistance were eligible for the analysis. T790M ctDNA was detected in the plasma of 55/117 (47%) patients. Almost half of the T790M ctDNA positive patients were identified at a median time of 2.2 months prior to clinically progressive disease (PD). Furthermore, within the patients receiving TKI treatment at 2nd line or later, the T790M ctDNA positive group had significantly shorter OS than the negative group (median OS: 26.9 months versus NA, P = 0.0489). Our study demonstrates the feasibility of monitoring EGFR mutation dynamics in serial plasma samples from NSCLC patients receiving TKI therapy. T790M ctDNA can be detected in plasma before and after PD as a poor prognostic factor.
Staphylococcus aureus isolates (n = 30) from the environment or from surgical patients in a hospital in Guangzhou, China were investigated for the presence of class 1 integrons. The class 1 integrase (intI1) gene and its 3' conserved segment were detected by PCR. IntI1-positive isolates were further analysed for the presence of resistance gene cassettes using specific primers, intI1-K and In-B. All isolates were also subjected to multilocus sequence typing (MLST) and random amplified polymorphic DNA (RAPD)-PCR analysis. Sixteen (53%) clinical and environmental isolates were positive for the class 1 integrase gene and were also found to possess the aadA2 gene. The 30 isolates were classified into six distinct genotypes by RAPD-PCR analysis: type A (n = 2); type B (n = 2); type C (n = 3); type D (n = 7); type E (n = 8); and type F (n = 8). All isolates belonged to the same sequence type (ST239) by MLST. These results indicated transmission of S. aureus between the environment and patients, as well as the probability of nosocomial infection.
This study extended the mutation spectrum of PK in the Chinese Han population and provided further evidence for the genetic basis of PK. We first identified MVD simultaneously responsible for porokeratosis palmaris et plantaris disseminate development and confirmed the genotype-phenotype correlations.
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