Clinical Significance of Pathogenicity of Somatic Mutations in Oral Leukoplakia: a Prospective Observational Study

Background. The vast majority of malignant neoplasms of the oral mucosa refer to squamous cell carcinomas. The development of squamous cell carcinoma of the oral mucosa is often promoted by previous potentially malignant diseases, with oral leukoplakia dominating among them.Objective. To determine the clinical significance of the pathogenicity of somatic mutations in oral mucosal leukoplakia.Methods. The study material included 24 samples of abnormal epithelium of the oral mucosa from leukoplakia patients. QIAamp DNA FFPE Tissue Kit (Qiagen, Germany) was used for deoxyribonucleic acid (DNA) extraction from the samples. DNA sequencing was performed using IlluminaNextSeq 550 sequencer and TruSight™ Oncology 500 DNA Kit For Use with NextSeq (Illumina, USA). All DNA extractions from biological samples, preparation and sequencing of DNA libraries were performed step-by-step in strict accordance with the guidelines provided with the respective reagent kits. Bioinformatics analysis was carried out using specific software Illumina Base Space (Illumina, USA) and Galaxy Project (The Galaxy Community, a non-profit international project) according to current guidelines. The desired power of the study accounted for 90%. Two Proportions Z test was performed by means of The Sample Size Calculation of Statistica 12 (StatSoft, Inc.) with the set option “one-tailed hypothesis”, because it was initially assumed that pathogenic (oncogenic) genetic variants occur in the tissue of oral leukoplakia much more frequently than in the human reference genome used for sequence alignment.Results. The pathogenic somatic mutations in the TP53, KRAS, APC, NRAs and BRAF genes, identified in this study, alone or in combination, are highly likely (hazard ratio 3000-11000) to be associated with the development of oral mucosal leukoplakia and low-grade epithelial dysplasia. The multiplicity of pathogenic and likely pathogenic genetic variants associated with epithelial dysplasia, as well as the fact that a number of variants do not occur in all patients, suggests that the same histotype of oral mucosal dysplasia may develop under the influence of different mutations.Conclusion. The pathogenic and likely pathogenic variants of the TP53, KRAS, APC, NRAS and BRAF genes, identified in this study, alone or in combination, are highly likely (hazard ratio 3000–11000) to be associated with the development of leukoplakia and low-grade epithelial dysplasia

Germline mutations in patients with oral mucosal leukoplakia and squamous cell carcinoma: a prospective observational study

Background. The number of studies devoted to the molecular genetics of oral mucosal leukoplakia and squamous cell carcinoma is small, while the obtained results are usually preliminary in nature. We can assume the existence of region-specific pathogenic genetic variants involved in the development of oral mucosal leukoplakia and squamous cell carcinoma. With the knowledge of such variants, it would become possible to develop PCR (polymerase chain reaction) and NGS (next-generation sequencing) test systems for the detection of clinically significant germline mutations.Objectives — to identify pathogenic germline genetic variants in patients with oral mucosal leukoplakia accompanied by grade 1 epithelial dysplasia, as well as oral mucosal squamous cell carcinoma, using new-generation sequencing.Methods. Study design: prospective, observational, cross-sectional, without a control group. The sample included patients (48 persons) of either sex (18 years of age or older) with the following proven and morphologically confirmed diagnoses: oral mucosal leukoplakia accompanied by grade 1 squamous intraepithelial neoplasia of epithelium (24 people) and oral mucosal squamous cell carcinoma (24 people), who sought medical care at the Vitebsk Regional Clinical Dental Center and Vitebsk Regional Clinical Oncological Center in 2019–2020. The identified pathogenic and presumably pathogenic genetic variants involved in the development of these diseases were quantitatively assessed. The study was conducted at the Shareable Core Facilities GENOME of the Institute of Genetics and Cytology of the National Academy of Sciences of Belarus. In order to isolate deoxyribonucleic acid (DNA) from blood samples, a QIAamp DNA FFPE Tissue Kit (Qiagen, Germany) was used. The preparation of DNA libraries and sequencing were carried out by means of an Illumina NextSeq 550 sequencing system (Illumina, Inc., USA) using an Illumina Nextera DNA Exome kit (USA). Bioinformatic analysis was conducted using Illumina BaseSpace specialized software (USA) and Galaxy Project (Galaxy Community, an international non-profit project) in accordance with current guidelines. The obtained data were statistically processed employing specialized software packages Statistica 12 (StatSoft, Inc., USA) and MedCalc 18.9.1 (MedCalc Software, Ltd, Belgium).Results. Next-generation whole-exome sequencing of deoxyribonucleic acid samples isolated from the blood of patients with oral mucosal leukoplakia and squamous cell carcinoma has been conducted in the Republic of Belarus for the first time. The total number of unique germline genetic variants in the exome of both groups of patients was shown to be very high, yet most of them were not pathogenic. In the examined patients, the majority of germline mutations were found to be localized only in 19 exome genes: MAP2K3, DNAH5, HSPG2, OBSCN, SYNE1, HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-A, HLA-B, PKD1L2, TTN, AHNAK2, PDE4DIP, MUC3A, MUC4, MUC12, MUC16, and MUC17. In both clinical groups, the greatest number of genetic variants (> 40% of the total number) was detected in MUC3A, MUC4, MUC12, and MUC16, responsible for the synthesis of the glycoprotein mucin family.Conclusion. Oral mucosal leukoplakia and squamous cell carcinoma can arise from the pathogenic variants of MUC3A, MUC4, MUC12, and MUC16

Methodology for generating a global forest management layer

The first ever global map of forest management was generated based on remote sensing data. To collect training data, we launched a series of Geo-Wiki (https://www.geo-wiki.org/) campaigns involving forest experts from different world regions, to explore which information related to forest management could be collected by visual interpretation of very high-resolution images from Google Maps and Microsoft Bing, Sentinel time series and normalized difference vegetation index (NDVI) profiles derived from Google Earth Engine. A machine learning technique was then used with the visually interpreted sample (280K locations) as a training dataset to classify PROBA-V satellite imagery. Finally, we obtained a global wall-to-wall map of forest management at a 100m resolution for the year 2015. The map includes classes such as intact forests; forests with signs of management, including logging; planted forests; woody plantations with a rotation period up to 15 years; oil palm plantations; and agroforestry. The map can be used to deliver further information about forest ecosystems, protected and observed forest status changes, biodiversity assessments, and other ecosystem-related aspects

Global forest management data for 2015 at a 100 m resolution

Spatially explicit information on forest management at a global scale is critical for understanding the status of forests, for planning sustainable forest management and restoration, and conservation activities. Here, we produce the first reference data set and a prototype of a globally consistent forest management map with high spatial detail on the most prevalent forest management classes such as intact forests, managed forests with natural regeneration, planted forests, plantation forest (rotation up to 15 years), oil palm plantations, and agroforestry. We developed the reference dataset of 226 K unique locations through a series of expert and crowdsourcing campaigns using Geo-Wiki (https://www.geo-wiki.org/). We then combined the reference samples with time series from PROBA-V satellite imagery to create a global wall-to-wall map of forest management at a 100 m resolution for the year 2015, with forest management class accuracies ranging from 58% to 80%. The reference data set and the map present the status of forest ecosystems and can be used for investigating the value of forests for species, ecosystems and their services

Modeling of diffraction of radio waves on obstacles

Разработаны методы, алгоритмы и комплекс программ для определения вида трассы распространения радиоволн, поиска препятствий на трассе и вычисления их характеристик, определения количества и координат точек преломления пути радиоволн, вычисления ослабления напряженности электромагнитного поля при дифракции радиоволн на препятствиях. Комплекс программ представлен в виде DLL-библиотеки и интерактивного исполняемого модуля. Алгоритмы и программы могут использоваться для моделирования дифракции радиоволн на препятствиях в автоматизированных системах планирования радиосвязи

Method of the rating of size of fading due to multipath beam spreading

Разработан метод, алгоритмы и комплекс программ для вычисления величины замираний радиосигнала из-за многолучевого распространения радиоволн, которая не будет превышена в среднем наихудшем месяце года в течение заданного процента времени. Комплекс программ представлен в виде DLL-библиотеки и интерактивного исполняемого модуля. Алгоритмы и программы могут использоваться в автоматизированных системах планирования радиосвязи