Cell death is an important part of normal (physiological) and pathological histogenesis. In the past two decades, our knowledge of the processes of non-programmed and programmed cell death significantly enriched. The International Nomenclature Committee on Cell Death is constantly working, it regularly updates information on the terminology and development mechanisms recommended for this or that type of death, but the general principle of classification of cell death has not yet been worked out. In this review, the principle of separation according to which the mechanisms involved in physiological histogenesis include the rooting, the external pathway of apoptosis, anoikis, macroautophagy and lysosome-dependent cell death. The mechanisms involved in pathological histogenesis include: the internal pathway of apoptosis, necroptosis, pyroptosis, netosis, mitotic catastrophe, partanatosis, entosis, mitochondrial-driven necrosis, ferroptosis, immunogenic cell death, necrosis and oncosis.

Background: Approximately 5–10% of all cancers are associated with hereditary cancer predisposition syndromes (HCPS). Early identification of HCPS is facilitated by widespread use of next-generation sequencing (NGS) and brings significant benefits to both the patient and their relatives. This study aims to evaluate the landscape of genetic variants in patients with personal and/or family history of cancer using NGS-based multigene panel testing. Materials and Methods: The study cohort included 1117 probands from Russia: 1060 (94.9%) patients with clinical signs of HCPS and 57 (5.1%) healthy individuals with family history of cancer. NGS analysis of 76 HCPS genes was performed using a custom Roche NimbleGen enrichment panel. Results: Pathogenic/likely pathogenic variants were identified in 378 of 1117 individuals (33.8%). The predominant number (59.8%) of genetic variants was identified in BRCA1/BRCA2 genes. CHEK2 was the second most commonly altered gene with a total of 28 (7.4%) variants, and 124 (32.8%) genetic variants were found in other 35 cancer-associated genes with variable penetrance. Conclusions: Multigene panel testing allows for a differential diagnosis and identification of high-risk group for oncological diseases. Our results demonstrate that inclusion of non-coding gene regions into HCPS gene panels is highly important for the identification of rare spliceogenic variants with high penetrance.

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