Purpose: While TP53 mutations are well known to be associated with adverse prognosis in hematological diseases, their functional impact remains incompletely understood. This study examines the spectrum of TP53 mutations across various hematologic malignancies and evaluates their functional impact. Materials and Methods: Using targeted sequencing panels, we analyzed TP53 mutations in the bone marrow aspiration samples of a retrospective cohort of 856 patients diagnosed with hematologic malignancies. To assess the impact of TP53 mutations, we applied the evolutionary action (EAp53) score and the relative fitness score (RFS), previously proposed functional scoring methods. The effects of variant allele frequency (VAF), disruptive mutations, EAp53 score, and RFS on overall survival (OS) were evaluated. Results: TP53 mutations were associated with inferior OS compared with wildtype TP53 (median OS 10.0 months versus not estimable; hazard ratio (HR) 4.6; p<0.001). In the acute myeloid leukemia, multiple myeloma, and myelodysplastic syndrome subgroups, TP53 mutations had a significant adverse impact on OS. (HRs 3.8, 4.2, 6.0, respectively; p<0.001, p=0.005, p<0.001, respectively). Patients with VAF >50% had significantly poorer OS compared to those with VAF ≤50% (median OS 7.5 months versus 22.8 months; HR 2.2, p=0.016). Moreover, patients in the high-risk RFS group (RFS >0.22) had significantly worse OS compared to those in the low-risk RFS group (RFS ≤0.22) (median OS 5.6 months versus 16.3 months; HR 2.2, p=0.041). However, no significant survival difference was observed between the EAp53 high-risk (>75) and low-risk (≤75) groups, or between patients with disruptive and non-disruptive mutations. Conclusion Our findings highlight VAF and RFS as valuable tools for stratifying TP53-mutant patients into high-risk and low-risk groups.

Purpose: Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer, with approximately 30% of patients eventually developing brain metastases (BM), which result in poor outcomes. An understanding of the tumor microenvironment (TME) at both primary and metastatic sites offers insights into the mechanisms underlying BM and potential therapeutic targets. Materials and Methods: Spatial RNA sequencing (spRNA-seq) was performed on primary TNBC and paired BM tissues from three patients, one of whom had previously received immune checkpoint inhibitors before BM diagnosis. Specimen regions were categorized into tumor, proximal, and distal TME based on their spatial locations. Gene expression differences across these zones were analyzed, and immune cell infiltration was estimated using TIMER. A gene module analysis was conducted to identify key gene clusters associated with BM. Results: Distinct gene expression profiles were noted in the proximal and distal TMEs. In BM, the proximal TME exhibited neuronal gene expression, suggesting neuron-tumor interactions compared to tumor, and upregulation of epithelial genes compared to the distal TME. Immune cell analysis revealed dynamic changes in CD8+ T cells and macrophages across the tumor and TME zones. Gene module analysis identified five key modules, including one related to glycolysis, which correlated with patient survival. Drug repurposing analysis identified potential therapeutic targets, including VEGFA, RAC1, EGLN3, and CAMK1D. Conclusion This study provides novel insights into the transcriptional landscapes in TNBC BM using spRNA-seq, emphasizing the role of neuron-tumor interactions and immune dynamics. These findings suggest new therapeutic strategies and underscore the importance of further research.

Background: As nationwide government-led whole-genome sequencing (WGS) projects progress, optimizing the clinical integration of large-scale WGS results is crucial. We explored how the initial analysis from Korea’s First WGS Pilot Study for Rare Diseases was applied in clinical practice, and then we reanalyzed the data comprehensively at Samsung Medical Center (SMC) Seoul, Korea. Methods: A prospective cohort study designed to collect WGS data under a Korean national initiative was conducted from August 2020 to December 2021. We focused on patients with rare diseases recruited from 16 university hospitals. The participants included 5,000 individuals (2,200 probands and 2,800 family members). The initial WGS data and diagnostic reference reports (from 682 probands and 484 family members), generated based on the First Korean WGS Pilot Study for Rare Diseases, were subsequently reanalyzed by SMC. Results: The initial analysis of the First Korean WGS Pilot Study data revealed a diagnostic rate of 17%. Upon receiving these results, the SMC conducted two rounds of reanalysis, increasing the diagnostic rate from 15% in the first analysis, to 18% in the second, and finally to 24% in the third (P = 1.6 × 10 −5 ). Key factors in improving the genetic diagnosis included increased detection of novel (likely) pathogenic variants (P = 1.0 × 10 −4 ), improved diagnostic rates with larger family recruitment (P = 0.004), and refined clinical information for more precise genotype–phenotype correlation analysis (40%). Conclusions Although national WGS projects lay a foundation for rare disease diagnosis, hospital-level reanalysis and multidisciplinary collaborations are crucial for optimizing diagnostic outcomes.

Purpose: Since 1995, the Korean Gastric Cancer Association (KGCA) has been periodically conducting nationwide surveys on patients with surgically treated gastric cancer. This study details the results of the survey conducted in 2023. Materials and Methods: The survey was conducted from March to December 2024 using a standardized case report form. Data were collected on 86 items, including patient demographics, tumor characteristics, surgical procedures, and surgical outcomes. The results of the 2023 survey were compared with those of previous surveys. Results: Data from 12,751 cases were collected from 66 institutions. The mean patient age was 64.6 years, and the proportion of patients aged ≥71 years increased from 9.1% in 1995 to 31.7% in 2023. The proportion of upper-third tumors slightly decreased to 16.8% compared to 20.9% in 2019. Early gastric cancer accounted for 63.1% of cases in 2023.Regarding operative procedures, a totally laparoscopic approach was most frequently applied (63.2%) in 2023, while robotic gastrectomy steadily increased to 9.5% from 2.1% in 2014.The most common anastomotic method was the Billroth II procedure (48.8%) after distal gastrectomy and double-tract reconstruction (51.9%) after proximal gastrectomy in 2023.However, the proportion of esophago-gastrostomy with anti-reflux procedures increased to 30.9%. The rates of post-operative mortality and overall complications were 1.0% and 15.3%, respectively. Conclusions The results of the 2023 nationwide survey demonstrate the current status of gastric cancer treatment in Korea. This information will provide a basis for future gastric cancer research.

Purpose: Since 1995, the Korean Gastric Cancer Association (KGCA) has been periodically conducting nationwide surveys on patients with surgically treated gastric cancer. This study details the results of the survey conducted in 2023. Materials and Methods: The survey was conducted from March to December 2024 using a standardized case report form. Data were collected on 86 items, including patient demographics, tumor characteristics, surgical procedures, and surgical outcomes. The results of the 2023 survey were compared with those of previous surveys. Results: Data from 12,751 cases were collected from 66 institutions. The mean patient age was 64.6 years, and the proportion of patients aged ≥71 years increased from 9.1% in 1995 to 31.7% in 2023. The proportion of upper-third tumors slightly decreased to 16.8% compared to 20.9% in 2019. Early gastric cancer accounted for 63.1% of cases in 2023.Regarding operative procedures, a totally laparoscopic approach was most frequently applied (63.2%) in 2023, while robotic gastrectomy steadily increased to 9.5% from 2.1% in 2014.The most common anastomotic method was the Billroth II procedure (48.8%) after distal gastrectomy and double-tract reconstruction (51.9%) after proximal gastrectomy in 2023.However, the proportion of esophago-gastrostomy with anti-reflux procedures increased to 30.9%. The rates of post-operative mortality and overall complications were 1.0% and 15.3%, respectively. Conclusions The results of the 2023 nationwide survey demonstrate the current status of gastric cancer treatment in Korea. This information will provide a basis for future gastric cancer research.

Purpose: Since 1995, the Korean Gastric Cancer Association (KGCA) has been periodically conducting nationwide surveys on patients with surgically treated gastric cancer. This study details the results of the survey conducted in 2023. Materials and Methods: The survey was conducted from March to December 2024 using a standardized case report form. Data were collected on 86 items, including patient demographics, tumor characteristics, surgical procedures, and surgical outcomes. The results of the 2023 survey were compared with those of previous surveys. Results: Data from 12,751 cases were collected from 66 institutions. The mean patient age was 64.6 years, and the proportion of patients aged ≥71 years increased from 9.1% in 1995 to 31.7% in 2023. The proportion of upper-third tumors slightly decreased to 16.8% compared to 20.9% in 2019. Early gastric cancer accounted for 63.1% of cases in 2023.Regarding operative procedures, a totally laparoscopic approach was most frequently applied (63.2%) in 2023, while robotic gastrectomy steadily increased to 9.5% from 2.1% in 2014.The most common anastomotic method was the Billroth II procedure (48.8%) after distal gastrectomy and double-tract reconstruction (51.9%) after proximal gastrectomy in 2023.However, the proportion of esophago-gastrostomy with anti-reflux procedures increased to 30.9%. The rates of post-operative mortality and overall complications were 1.0% and 15.3%, respectively. Conclusions The results of the 2023 nationwide survey demonstrate the current status of gastric cancer treatment in Korea. This information will provide a basis for future gastric cancer research.

Background: This study investigates the association between serum iron levels and frequency-specific hearing loss in Korean female population, a topic previously unexplored in auditory health research. Methods: This study enrolled Korean female participants from the general population. Serum iron levels and hearing thresholds at low (1 kHz) and high (4 kHz) frequencies were assessed, adjusting for potential confounders. Participants were stratified into quartiles based on serum iron levels. Results: The mean age of the study population was 51.1 ± 10.1 years. Among the 2,987 participants, 344 (11.5%) had abnormal low-frequency hearing thresholds, and 719 (24.1%) had abnormal high-frequency thresholds. Multiple linear regression analysis demonstrated a significant negative association between serum iron levels and low-frequency hearing thresholds (β = –0.012, p = 0.017), whereas no significant association was observed with high-frequency thresholds (β = –0.006, p = 0.352). In a stratified analysis using 50 years (the average menopausal age) as a cutoff, no statistically significant association was identified in participants younger than 50 years. However, in those aged 50 years and older, the negative association between serum iron levels and low-frequency hearing thresholds remained statistically significant. Conclusions This study is the first to identify an association between serum iron levels and low-frequency hearing loss in females aged 50 years and older, underscoring the potential role of iron in auditory function. These findings highlight the importance of further research in diverse populations to elucidate the underlying mechanisms and broader clinical implications.