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Pancreatic neuroendocrine tumors (NETs) are rare well-differentiated neoplasms with limited therapeutic options and unknown cells of origin. The current classification of pancreatic neuroendocrine tumors is based on proliferative grading, and guides therapeutic strategies, however, tumors within grades exhibit profound heterogeneity in clinical manifestation and outcome. Manifold studies have highlighted intra-patient differences in tumors at the genetic and transcriptomic levels. Molecular classification might become an alternative or complementary basis for treatment decisions and reflect tumor biology, actionable cellular processes. Here, we provide a comprehensive review of genomic, transcriptomic, proteomic and epigenomic studies of pancreatic NETs to elucidate patterns shared between proposed subtypes that could form a foundation for new classification. We denote four NET subtypes with distinct molecular features, which were consistently reproduced using various omics technologies. [ABSTRACT FROM AUTHOR]

The gut microbiota's pivotal role in human health is increasingly evident, particularly in chronic conditions like obesity, diabetes, and inflammatory diseases. This intricate symbiotic relationship influences metabolic balance and immune responses. Notably, gut microbial dysbiosis is linked to obesity's metabolic disruption and chronic low-grade inflammation. Similarly, in diabetes, the microbiota's impact on insulin resistance and glucose metabolism is becoming evident. Chronic inflammation, a common denominator in these conditions, is also a recognized precursor to carcinogenesis. This intersection prompts a compelling question: does the gut microbiota's influence extend to gastrointestinal cancers like colorectal and pancreatic cancer? These malignancies are closely intertwined with inflammation and metabolic dysregulation. Exploring whether the microbial signatures associated with chronic conditions overlap with precancerous or cancerous states offers new perspectives. This article reviews emerging evidence on the interplay between the gut microbiota, chronic conditions, and gastrointestinal cancers. By elucidating these connections, we aim to uncover potential avenues for innovative diagnostic, preventative, and therapeutic strategies in colorectal and pancreatic cancer management. [ABSTRACT FROM AUTHOR]

The extraocular muscles (EOMs) possess unique characteristics that set them apart from other skeletal muscles. These muscles, responsible for eye movements, exhibit remarkable resistance to various muscular dystrophies and aging, presenting a significant contrast to the vulnerability of skeletal muscles to these conditions. In this review, we delve into the cellular and molecular underpinnings of the distinct properties of EOMs. We explore their structural complexity, highlighting differences in fiber types, innervation patterns, and developmental origins. Notably, EOM fibers express a diverse array of myosin heavy-chain isoforms, retaining embryonic forms into adulthood. Moreover, their motor innervation is characterized by a high ratio of nerve fibers to muscle fibers and the presence of unique neuromuscular junctions. These features contribute to the specialized functions of EOMs, including rapid and precise eye movements. Understanding the mechanisms behind the resilience of EOMs to disease and aging may offer insights into potential therapeutic strategies for treating muscular dystrophies and myopathies affecting other skeletal muscles. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndrome (MDS) is a clonal disease derived from hematopoietic stem cells, characterized by ineffective hematopoiesis (resulting in peripheral blood cytopenia) and an increased risk of transformation into acute myeloid leukemia. MDS is caused by a complex combination of genetic mutations resulting in a heterogeneous genotype. Genetic studies have identified a set of aberrations that play a central role in the pathogenesis of MDS. In this article, we present a clinical case of MDS transformation into acute myeloid leukemia in the context of two cell lines exhibiting morphological, immunophenotypic, and dysmyelopoiesis markers and the presence of two heterozygous mutations in the TET2 gene. [ABSTRACT FROM AUTHOR]

Simple Summary: This study addresses the global healthcare challenge of cancer by investigating hereditary cancer syndromes (HCS) and their genetic underpinnings. Using a multigene hereditary cancer panel, we examined Russian patients with suspected HCS, revealing that 21.6% had pathogenic or likely pathogenic genetic variants. Predominant mutations were found in BRCA1/BRCA2, CHEK2, and ATM genes, and we identified 16 previously undescribed variants in MUTYH, GALNT12, MSH2, MLH1, MLH3, EPCAM, and POLE genes. Our findings underscore the importance of comprehensive genetic testing for personalized cancer prevention and treatment. This research contributes essential genetic insights, particularly in regions like Russia where epidemiological data are limited, establishing the way for improved understanding and management of hereditary cancer syndromes. Cancer is a major global public health challenge, affecting both quality of life and mortality. Recent advances in genetic research have uncovered hereditary cancer syndromes (HCS) that predispose individuals to malignant neoplasms. While traditional single-gene testing has focused on high-penetrance genes, the past decade has seen a shift toward multigene panels, which facilitate the analysis of multiple genes associated with specific HCS. This approach reveals variants in less-studied gene regions and improves our understanding of cancer predisposition. In a study composed of Russian patients with clinical signs of HCS, we used a multigene hereditary cancer panel and revealed 21.6% individuals with pathogenic or likely pathogenic genetic variants. BRCA1/BRCA2 mutations predominated, followed by the CHEK2 and ATM variants. Of note, 16 previously undescribed variants were identified in the MUTYH, GALNT12, MSH2, MLH1, MLH3, EPCAM, and POLE genes. The implications of the study extend to personalized cancer prevention and treatment strategies, especially in populations lacking extensive epidemiological data, such as Russia. Overall, our research provides valuable genetic insights that give the way for further investigation and advances in the understanding and management of hereditary cancer syndromes. [ABSTRACT FROM AUTHOR]