Somatic and germline mutations in endometrial cancer.

Endometrial cancer is a complex disease influenced by both somatic and germline mutations. While individual mutations in genes such as PTEN, PIK3CA, and members of the DNA mismatch repair (MMR) system have been extensively studied, comprehensive analyses comparing somatic and germline mutations within the same cohort are limited. This study compares these mutations using whole exome sequencing (WES) data from tumor and blood samples in patients with endometrial cancer. Thirteen female patients with histologically confirmed endometrial cancer were selected. Tumor tissues and matched blood samples were collected and subjected to WES at the CeGaT laboratory, followed by bioinformatics analysis and annotation using the Geneyx platform. WES revealed significant somatic and germline DNA mutations, with key pathogenic variants identified in genes such as PTEN, PIK3CA, TP53, MLH1, and MSH2. Comparative analysis showed distinct and overlapping mutation profiles, highlighting the importance of integrating somatic and germline data in endometrial cancer research.

Lynch Syndrome-associated Genomic Variants.

BACKGROUND AND AIMS: Lynch Syndrome, a hereditary disorder characterized by germline mutations in mismatch repair (MMR) genes, is a major contributor to colorectal cancers. It has also been identified in endometrial cancer. Despite the established role of MMR deficiency in tumorigenesis, the specific genomic alterations driving Lynch syndrome-associated endometrial cancer, and their overlap with colorectal cancer, remain incompletely understood. This study aims to fill this gap by performing a detailed comparative analysis of germline and somatic mutations in endometrial cancer within the context of Lynch syndrome. METHODS: We conducted whole exome sequencing on matched germline and somatic DNA from 13 patients diagnosed with Lynch syndrome-associated endometrial cancer. High-depth sequencing was performed, followed by rigorous bioinformatics analysis to identify and annotate variants, focusing on their potential pathogenicity and relevance to both endometrial and colorectal cancer. RESULTS: Our analysis revealed 1,118 germline and 14,051 somatic variants, with 493 variants common to both. Recurrent pathogenic mutations in MLH1, MSH2, and MSH6 were confirmed, highlighting their critical role in Lynch syndrome. Notably, frequent somatic mutations in the PIK3CA and PTEN genes were identified, implicating the PI3K/AKT/mTOR pathway as a key oncogenic driver in these cancers. Additionally, novel somatic mutations in genes related to the extracellular matrix such as FBN1 and SPARC were uncovered, suggesting a possible unique role in endometrial tumor progression. CONCLUSIONS: This study provides new insights into the molecular basis of Lynch syndrome-associated endometrial cancer, emphasizing the overlap in oncogenic pathways with colorectal cancer. The discovery of shared and unique genetic mutations highlights the importance of developing combined treatment strategies and suggests that targeting these specific mutations could improve therapy for patients with Lynch syndrome-associated cancers.

Designing the future of prenatal care: an algorithm for a telemedicine-enhanced team-based care model.

This study provides a conceptual exploration of an innovative telemedicine-enhanced team-based care (TETC) model, tailored to prenatal care, integrating a multidisciplinary team approach with advanced telemedicine technologies. The algorithm developed for TETC aims to optimize communication and coordination among healthcare professionals, including obstetricians, midwives, nutritionists, and mental health experts. This cohesive team structure ensures a comprehensive care plan encompassing all facets of maternal and fetal health. Leveraging telemedicine tools like video conferencing and digital health records, the model supports remote consultations and coordinated care, proving particularly advantageous during pandemics or in regions with limited healthcare access. Central to the TETC model is patient-centered care, focusing on personalized care plans attuned to the individual needs, health status, and socioeconomic backgrounds of pregnant women. This approach not only enhances accessibility and convenience by diminishing the necessity for physical consultations but also ensures continuity of care throughout pregnancy. This continuity is crucial for consistent health parameter tracking and early risk identification. The paper discusses the model's design, operational workflow, and ethical and legal considerations, providing implementation guidelines and potential applications. The TETC model, rooted in current technological capabilities and healthcare frameworks, underscores the need for close collaboration with healthcare professionals to adhere to medical standards and address real-world requirements effectively.

Pregnancy and umbilical cord pathology: structural and functional parameters of the umbilical cord.

Scientific research in the field of physiology and pathology of the umbilical cord is quite limited and imperfect. The purpose of the study was to evaluate the histological architecture of the pathological umbilical cord and investigate the relationship between the main parameters and placental postnatal macromorphometric characteristics, which serve as a reflection of placental dysfunction. Four groups of patients were included, each undergoing a postnatal histological and topographic examination of the umbilical cord: Wharton's jelly edema (10 samples), velamentous cord insertion (10 samples), single umbilical artery (10 samples), and physiological pregnancy (10 samples). Compared to the control group, all newborn groups exhibited changes in umbilical vessel morphology, characterized by an increased Wagenworth index and a decreased Kernohan index. The functional indices of the umbilical vessels were found to be most severely affected in cases of Wharton's jelly edema. In cases of single umbilical artery, the changes in vascular functional parameters indicated their compensatory remodeling with the highest Wagenworth and Kernohan indices of the umbilical vein. Deviation from the normal average placental weight was observed in cases of Wharton's jelly volume pathology or velamentous cord insertion. However, in the case of a single umbilical artery, there were no significant deviations in the macromorphometry of the placenta.