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Purpose: Early detection and intervention can decrease the mortality of breast cancer significantly. Assessments of genetic/genomic variants in circulating tumor DNA (ctDNA) have generated great enthusiasm for their potential application as clinically actionable biomarkers in the management of early-stage breast cancer. Experimental Design: In this study, 861 serial plasma and matched tissue specimens from 102 patients with early-stage breast cancer who need chemotherapy and 50 individuals with benign breast tumors were deeply sequenced via next-generation sequencing (NGS) techniques using large gene panels. Results: Cancer tissues in this cohort of patients showed profound intratumor heterogeneities (ITHGs) that were properly reflected by ctDNA testing. Integrating the ctDNA detection rate of 74.2% in this cohort with the corresponding predictive results based on Breast Imaging Reporting and Data System classification (BI-RADS) could increase the positive predictive value up to 92% and potentially dramatically reduce surgical overtreatment. Patients with positive ctDNA after surgery showed a higher percentage of lymph node metastasis, indicating potential recurrence and remote metastasis. The ctDNA-positive rates were significantly decreased after chemotherapy in basal-like and Her2+ tumor subtypes, but were persistent despite chemotherapy in luminal type. The tumor mutation burden in blood (bTMB) assessed on the basis of ctDNA testing was positively correlated with the TMB in tumor tissues (tTMB), providing a candidate biomarker warranting further study of its potentials used for precise immunotherapy in cancer. Conclusions: These data showed that ctDNA evaluation is a feasible, sensitive, and specific biomarker for diagnosis and differential diagnosis of patients with early-stage breast cancer who need chemotherapy.

Genotyping epidermal growth factor receptor (EGFR) gene in patients with advanced non-small cell lung cancers (NSCLC) is essential for identifying those patients who may benefit from targeted therapies. Systemically evaluating EGFR mutation detection rates of different methods currently used in clinical setting will provide valuable information to clinicians and laboratory scientists who take care of NSCLC patients. This study retrospectively reviewed the EGFR data obtained in our laboratory in last 10 years. A total of 21,324 NSCLC cases successfully underwent EGFR genotyping for clinical therapeutic purpose, including 5,244 cases tested by Sanger sequencing, 13,329 cases tested by real-time PCR, and 2,751 tested by next-generation sequencing (NGS). The average EGFR mutation rate was 45.1%, with 40.3% identified by Sanger sequencing, 46.5% by real-time PCR and 47.5% by NGS. Of these cases with EGFR mutations identified, 93.3% of them harbored a single EGFR mutation (92.1% with 19del or L858R, and 7.9% with uncommon mutations) and 6.7% harbored complex EGFR mutations. Of the 72 distinct EGFR variants identified in this study, 15 of them (single or complex EGFR mutations) were newly identified in NSCLC. For these cases with EGFR mutations tested by NGS, 65.3% of them also carried tumor-related variants in some non-EGFR genes and about one third of them were considered candidates of targeted drugs. NGS method showed advantages over Sanger sequencing and real-time PCR not only by providing the highest mutation detection rate of EGFR but also by identifying actionable non-EGFR mutations with targeted drugs in clinical setting.

e13637 Background: Genotyping epidermal growth factor receptor ( EGFR) gene in patients with advanced non-small cell lung cancers (NSCLC) is essential to identify those patients who may benefit from targeted treatments. However, the testing methodology is still a puzzle for many clinicians. This study retrospectively reviewed the EGFR data from testing patients with NSCLC in our laboratory in 10 years. Methods: A total of 21,324 NSCLC cases successfully underwent EGFR genotyping in our laboratory for clinical therapeutic purpose, including 5,244 cases tested by Sanger sequencing, 13,329 cases tested by real-time PCR, and 2,751 tested by next generation sequencing-NGS. Results: 54.6%, 20% and 2.3% samples were recorded with tumor cell content (TCC) of < 40%, < 20% and 1% respectively. The average EGFR mutation rate was 45.1%, with 40.3% identified by Sanger sequencing, 46.5% by real-time PCR and 47.5% by NGS. Comparable EGFR mutation rates were observed in cases with 1%-20% TCC from real-time PCR and NGS platforms. In these cases with EGFR mutations, 93.3% of them carried a single EGFR mutation (92.1% with a classical mutation as 19del or L858R, and 7.9% with an uncommon mutation) and 6.7% harbored complex EGFR mutations. 65.3% of the cases carrying EGFR mutations identified by NGS also have tumor related variants in other genes. 26.5% more cases were found to have oncogenic driver mutations with therapeutic significance beyond EGFR by NGS. Conclusions: NGS may be the most optimal methodology to detect EGFR mutations in patients with NSCLC compared with Sanger sequencing and real-time PCR platforms from accuracy and comprehensiveness aspects, but some other issues, such as Turn Around Time (TAT), still should be considered in clinical practice.

Acid-doped polybenzimidazole membranes with good electrochemical properties at high temperatures have been under increasing study in recent years for application in high temperature polymer electrolyte membrane fuel cells. The disadvantages associated with these types of membranes include reduced mechanical properties due to doping and acid leaching under continuous usage. The aforementioned drawbacks can be partly overcome by the addition of modified inorganic nanoparticles. This work reports the synthesis of poly(2,5-benzimidazole) (ABPBI) membranes and fabrication of ABPBI–silica nanocomposites by an ex situ technique using methanesulfonic acid as the solvent. The introduction of sulfonated silica nanoparticles into the ABPBI matrix helps to improve the water uptake, proton conductivity, thermal stability and mechanical property of the nanocomposites compared to the virgin ABPBI membrane. The storage modulus of phosphoric acid-doped ABPBI (dABPBI) nanocomposite with 10 wt% modified silica is increased by 2-fold compared to that of virgin dABPBI. The maximum proton conductivity of 38.01 mS cm −1 is obtained from dABPBI nanocomposite membrane containing 10 wt% modified silica at 140 °C and 1% relative humidity in comparison to 15.23 mS cm −1 for virgin dABPBI membrane under similar conditions.

e23066Background: Molecular profiling for CRC commonly utilizes tissue, however, there are two major limitations. It is hard to overcome the complications of tumor heterogeneity and inconvenient to...