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Simple Summary: Nasopharyngeal carcinoma (NPC) is extremely frequent in several regions of the world, particularly Southern China (known as the Cantonese cancer). Previous studies were often limited to small cohorts, and systematic comparison with other cancer types has not been explored. In this study, we collected the largest NPC cohort (n = 431) and provided the first integrative analysis of NPC genomes. We identified many novel drivers and mutational signatures in NPC. By comparing NPC with other cancer types, we discovered many unique processes driving a viral-positive cancer type. As one of few viral-positive cancers, nasopharyngeal carcinoma (NPC) is extremely rare across the world but very frequent in several regions of the world, including Southern China (known as the Cantonese cancer). Even though several genomic studies have been conducted for NPC, their sample sizes are relatively small and systematic comparison with other cancer types has not been explored. In this study, we collected four-hundred-thirty-one samples from six previous studies and provided the first integrative analysis of NPC genomes. Combining several statistical methods for detecting driver genes, we identified 25 novel drivers for NPC, including ATG14 and NLRC5. Many of these novel drivers are enriched in several important pathways, such as autophagy and immunity. By comparing NPC with many other cancer types, we found NPC is a unique cancer type in which a high proportion of patients (45.2%) do not have any known driver mutations (termed as "missing driver events") but have a preponderance of deletion events, including chromosome 3p deletion. Through signature analysis, we identified many known and novel signatures, including single-base signatures (n = 12), double-base signatures (n = 1), indel signatures (n = 9) and copy number signatures (n = 8). Many of these new signatures are involved in DNA repair and have unknown etiology and genome instability, implying an unprecedented dynamic mutational process possibly driven by complex interactions between viral and host genomes. By combining clinical, molecular and intra-tumor heterogeneity features, we constructed the first integrative survival model for NPC, providing a strong basis for patient prognosis and stratification. Taken together, we have performed one of the first integrative analyses of NPC genomes and brought unique genomic insights into tumorigenesis of a viral-driven cancer. [ABSTRACT FROM AUTHOR]

Background and Aims: The global obesity epidemic is growing worldwide and its further growth is expected in the future. In obesity, the formation of reactive oxygen species (ROS) and cytokines is normally observed, which damage the genetic material. The purpose of this study was to assess lymphocyte DNA damage before and after metformin use in obese individuals., Novelty: The novelty of the article is that for the first time DNA damage in lymphocytes before and after the use of metformin in obese individuals among Kazakh population was studied., Methods: Indirect immunofluorescence analysis using the AKLIDES apparatus was used for the quantitative determination of phosphorylated γ-H2AX (Ser 139) and 53BP1 in order to analyze DNA breaks in the lymphocytes., Results: The data indicating premature cell aging in the visceral adipose tissue in obese individuals were obtained. An increased hypoxia was observed in combination with an increase in γ-H2AX foci. DNA damage monitoring may become an important part of clinical studies of obesity. Advanced methods to diagnose obesity with early detection of precancerous changes imply a personalized approach, which is ineffective without data from genomic studies., Conclusion: This study showed that metformin at a dose of 850 mg/day for 3 months for the treatment of obesity (BMI more than 30 kg/m 2 ) resulted in a decrease in DNA breaks in the lymphocytes., (Copyright © 2022 Diabetes India. Published by Elsevier Ltd. All rights reserved.)