No abstract

Next-generation sequencing (NGS) technology has improved enough to discover mutations associated with genetic diseases. Our study evaluated the feasibility of targeted NGS as a primary screening tool to detect causal variants and subsequently predict genetic diseases. We performed parallel computations on 3.7-megabase-targeted regions to detect disease-causing mutations in 103 participants consisting of 81 patients and 22 controls. Data analysis of the participants took about 6 hours using local databases and 200 nodes of a supercomputer. All variants in the selected genes led on average to 3.6 putative diseases for each patient while variants restricted to disease-causing genes identified the correct disease. Notably, only 12% of predicted causal variants were recorded as causal mutations in public databases: 88% had no or insufficient records. In this study, most genetic diseases were caused by rare mutations and public records were inadequate. Most rare variants, however, were not associated with genetic diseases. These data implied that novel, rare variants should not be ignored but interpreted in conjunction with additional clinical data. This step is needed so appropriate advice can be given to primary doctors and parents, thus fulfilling the purpose of this method as a primary screen for rare genetic diseases.

The molecular features of mantle cell lymphoma (MCL), including its increased incidence, and complex therapies have not been investigated in detail, particularly in East Asian populations. In this study, we performed targeted panel sequencing (TPS) and whole-exome sequencing (WES) to investigate the genetic alterations in Korean MCL patients. We obtained a total of 53 samples from MCL patients from five Korean university hospitals between 2009 and 2016. We identified the recurrently mutated genes such as SYNE1, ATM, KMT2D, CARD11, ANK2, KMT2C, and TP53, which included some known drivers of MCL. The mutational profiles of our cohort indicated genetic heterogeneity. The significantly enriched pathways were mainly involved in gene expression, cell cycle, and programmed cell death. Multivariate analysis revealed that ANK2 mutations impacted the unfavourable overall survival (hazard ratio [HR] 3.126; P = 0.032). Furthermore, TP53 mutations were related to worse progressionfree survival (HR 7.813; P = 0.043). Among the recurrently mutated genes with more than 15.0% frequency, discrepancies were found in only 5 genes from 4 patients, suggesting comparability of the TPS to WES in practical laboratory settings. We provide the unbiased genetic landscape that might contribute to MCL pathogenesis and recurrent genes conferring unfavourable outcomes. Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin's lymphoma (NHL) accounting for 5-7% of all NHLs 1. Although MCL is uncommon (0.64/100,000 person-years), there has been a 130.9% rise in its incidence in recent years 2. Higher incidence rates have been seen in Caucasians (153.0%), Asians (96.

This paper presents a method of fabricating pulverized drug, Lapatinib (Tykerb®), loaded micro chambers made of a biodegradable polymer, poly (£-caprolactone) (PCL), for bacteria-based microrobots. The PCL is a biodegradable, biocompatible polymer which is approved by the U.S. Food and Drug Administration (FDA) for use in the implantable medical devices. Lapatinib is approved by the U.S. FDA for the treatment of advanced or metastatic breast cancer. In order to realize bacteria-based microrobots, selective bacterial adhesion is necessary which can enhance directional locomotion of the bacteria-based microrobots. The x-ray lithography process can be used for biodegradable polymer micromachining to fabricate structures with various shapes which can be applied for bacteria-based microrobots. A pulverized drug is used because a liquefied drug cannot be used for the x-ray lithography process. To fabricate pulverized Lapatinib loaded micro chambers, the PCL films are prepared by the solvent casting method and lamination process. Lapatinib is encapsulated between the PCL films by the screen printing method. The x-ray lithography process is then used for fabrication of micro chambers. The fabrication results indicate that the proposed method is appropriate for fabrication of biodegradable polymeric micro chambers encapsulated with the pulverized drug for bacteria-based microrobots.