Context Head and neck paragangliomas (HNPGLs) are rare neoplasms with a high degree of heritability. Nevertheless, paragangliomas present as polygenic diseases caused by combined alterations in multiple genes, however, many driver changes remain unknown. Objective The objective of the study was to analyze somatic mutation profiles in HNPGLs. Design Whole-exome sequencing of 42 tumors and matched normal tissues obtained from Russian patients with HNPGLs was carried out. Somatic mutation profiling included variant calling and utilizing of MutSig and SigProfiler packages. Results 57% of patients harbored germline and somatic variants in the PGL susceptibility genes or potentially related genes. Somatic variants in novel genes were found in 17% of patients without mutations in any known PGL-related genes. The studied cohort was characterized by six significantly mutated genes: SDHD, BCAS4, SLC25A14, RBM3, TP53, and ASCC1, as well as four COSMIC SBS-96 mutational signatures (SBS5, SBS29, SBS1, and SBS7b). Tumors with germline variants specifically displayed SBS11 and SBS19, when SBS33 specific mutational signature was identified for cases without those. B allele frequency analysis of copy number variations revealed loss of heterozygosity of the wild-type allele in one patient with germline mutation c.287-2A>G in the SDHB gene. In patients with germline mutation c.A305G in the SDHD gene, frequent potential loss of chromosome 11 was observed. Conclusion These results give an understanding of somatic changes and the mutational landscape associated with HNPGLs and are important for the identification of molecular mechanisms involved in tumor development.

Castration-resistant prostate cancer (CRPC) is a common form of prostate cancer in which docetaxel-based chemotherapy is used as the first line. The present study is devoted to the analysis of transcriptome profiles of tumor cells in the development of resistance to docetaxel as well as to the assessment of the combined effect with the XAV939 tankyrase inhibitor on maintaining the sensitivity of tumor cells to chemotherapy. RNA-Seq was performed for experimental PC3 cell lines as well as for plasma exosome samples from patients with CRPC. We have identified key biological processes and identified a signature based on the expression of 17 mRNA isoforms associated with the development of docetaxel resistance in PC3 cells. Transcripts were found in exosome samples, the increased expression of which was associated with the onset of progression of CRPC during therapy. The suppression of pathways associated with the participation of cellular microtubules has also been shown when cells are treated with docetaxel in the presence of XAV939. These results highlight the importance of further research into XAV939 as a therapeutic agent in the treatment of CRPC; moreover, we have proposed a number of mRNA isoforms with high predictive potential, which can be considered as promising markers of response to docetaxel.

Annual killifish of the genus Nothobranchius are seeing a rapid increase in scientific interest over the years. A variety of aspects surrounding the egg-laying Cyprinodontiformes is being extensively studied, including their aging. Inhabiting drying water bodies of Africa rarely allows survival through more than one rainy season for the Nothobranchius populations. Therefore, there is no lifespan-related bias in natural selection, which has ultimately led to the decreased efficiency of DNA repair system. Aging of the Nothobranchius species is studied both under normal conditions and under the influence of potential geroprotectors, as well as genetic modifications. Most biogerontological studies are conducted using the species Nothobranchiusfurzeri (GRZ isolate), which has a lifespan of 3 to 7 months. However, the list of model species of Nothobranchius is considerably wider, and the range of advanced research areas with their participation extends far beyond gerontology. This review summarizes the most interesting and promising topics developing in the studies of the fish of Nothobranchius genus. Both classical studies related to lifespan control and rather new ones are discussed, including mechanisms of diapause, challenges of systematics and phylogeny, evolution of sex determination mechanisms, changes in chromosome count, occurrence of multiple repeated DNA sequences in the genome, cognitive and behavioral features and social stratification, as well as methodological difficulties in working with Nothobranchius.

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