Background/Objectives: Breast cancer (BCa) is a heterogeneous disease with molecular and genetic characteristics that significantly influence prognosis and treatment strategies. Age-related differences in tumor biology may impact therapeutic decisions; however, data on somatic mutation profiles in geriatric patients are limited. Methods: This retrospective study included 371 BCa patients (53 geriatric ≥ 65 years, 318 non-geriatric) whose clinicopathological and next-generation sequencing (NGS) data were analyzed. Immunohistochemical markers and molecular subtypes were assessed according to ASCO/CAP guidelines. Mutational profiles were obtained using the QIAseq Human BCa Panel (93 genes). Results: Among all patients, 1669 somatic mutations were detected, and 93.3% of patients harbored at least one mutation. Mutation prevalence was similar between geriatric (96.2%) and non-geriatric (92.8%) groups (p = 0.526), indicating that age did not significantly affect overall mutational burden. The most frequently mutated genes were ATR, TP53, PIK3CA, PTEN, RAD50, BLM, NF1, AR, BRCA2, and KMT2C. Notably, PIK3CA mutations were significantly more frequent in geriatric patients (28.3% vs. 23.2%, p = 0.0418). TP53 mutations correlated with higher Ki-67 proliferation indices (p = 0.035), while ATR mutations were more common in HER2-enriched subtypes (p = 0.002). Conclusions: Our findings indicate that while the overall somatic mutational load in BCa does not differ significantly with age, specific molecular alterations—particularly the enrichment of PIK3CA mutations in elderly patients—underscore the importance of integrating genomic profiling into personalized treatment planning. This study represents the first comprehensive molecular characterization of geriatric BCa patients in Türkiye, providing valuable insights for age-specific genetic profiling, treatment optimization, and future multicenter translational studies.

The prognostic significance of next-generation sequencing (NGS) findings during the hormone-sensitive phase of prostate cancer remains incompletely characterized. This retrospective cohort study included 92 patients who underwent NGS analysis on tumor tissue between 2019 and 2025. The primary endpoint was time to castration-resistant prostate cancer (CRPC) from androgen deprivation therapy (ADT) initiation; secondary endpoints were overall survival from ADT initiation (OS-ADT) and from diagnosis. Kaplan-Meier and Cox regression analyses were performed. CRPC developed in 66 patients (71.7%) at a median of 21.1 months. The most frequently altered genes were ATR (35.9%), PTEN (28.3%), TP53 (26.1%), and BRCA2 (15.2%). KMT2C alteration (5.4%) was the strongest independent genomic predictor of shorter time to CRPC (HR = 6.804, p = 0.003) and OS-ADT (HR = 4.730, p = 0.019). TP53 alteration independently predicted shorter OS-ADT (HR = 1.810, p = 0.038). High genomic burden independently predicted shorter time to CRPC (HR = 1.917, p = 0.032). Homologous recombination repair deficiency was not associated with outcomes, attributable to high ATR alteration frequency introducing pathway heterogeneity. Mismatch repair deficiency showed a borderline association with shorter OS-ADT (20.7 vs. 44.0 months; p = 0.060). An exploratory composite risk score stratified patients into three prognostic groups with markedly different outcomes (HR = 7.904, p = 0.001). NGS analysis during the hormone-sensitive phase identifies independent predictors of castration resistance, supporting its integration at ADT initiation for risk stratification and biomarker-guided treatment planning.

Amaç: Kemik iliği kor biyopsileri, kemik iliğinin hücresel özelliklerini, solid organ tümörü metastazlarını veya hematolojik malign tutulumlarını belirlemek için yapılan önemli incelemelerdir. Kor biyopsinin uzunluğu ve kalitesi doğru tanı konulmasını ve klinik süreci etkilemektedir. Bu çalışmada kemik iliği kor biyopsi uzunluğunun tanı sürecine olan etkisinin araştırılması amaçlanmıştır. Gereç ve Yöntem: Çalışmamızda bölümümüze son bir yıl içerisinde gelmiş olan kemik iliği biyopsi materyallerinin uzunlukları ve içerdikleri intertrabeküler alanlar mikroskop altında incelenmiş ve uzunlukları milimetre cinsinden ölçülmüştür. Kor biyopsiler; uzunlukları 15 milimetreye eşit ve/veya üzerinde ise yeterli grup, 15 milimetrenin altında ise yetersiz grup şeklinde iki gruba ayrılmıştır. Bulgular: Kor biyopsi uzunluğu 185 olguda (%48,9) yeterliydi. 194 olguda (%51,1) ise kemik iliği kor biyopsi uzunluğu 15 mm altında ölçüldü. Olguların 192 (%50,5) tanesine spesifik tanı (Miyeloproliferatif Neoplazi, Lenfoma tutulumu, Lösemi tanısı ve benzeri) konuldu. 188 olgunun (%49,5) ise selülaritesi değerlendirip görülen bulgular özetlendi. Spesifik tanı konabilen 192 olgunun 116 tanesinde (%62,4) biyopsi uzunluğu yeterli iken, spesifik tanı konulamayan 188 olgunun 118'inde (%62,8) biyopsi uzunluğu yetersizdi. Kor biyopsi uzunluğu ile spesifik tanı konulması arasında doğrudan kuvvetli bir ilişki vardı (p≤0,01). Sonuç: Kemik iliği kor biyopsi materyalleri güvenilir tanı için optimal büyüklükte alınmalı ve aspirasyon yaymaları ile birlikte değerlendirilmelidir. Ayrıca klinikopatolojik iş birliği tanı güvenirliğini artırmaktadır.

Background/Objectives: Endometrial cancer is a heterogeneous malignancy that displays distinct molecular features and clinical behaviors. The molecular profile of endometrial cancer and its relationship with menopausal status, histological subtype, tumor grade, mismatch repair (MMR)/microsatellite instability (MSI) status, co-mutation patterns, and TCGA molecular classification were investigated in the current study. Methods: A total of 81 histopathologically confirmed endometrial cancer cases were retrospectively evaluated. Molecular profiling was performed using a targeted 71-gene NGS panel together with MSI-PCR and mismatch repair (MMR) immunohistochemistry. Because the targeted panel was not designed to detect genome-wide copy-number alterations or comprehensive mutational signatures, molecular subgroup assignment was performed using a surrogate TCGA-inspired molecular classification approach based on POLE mutation status, microsatellite instability (MSI)/Mismatch Repair (MMR) findings, and TP53 alterations. Histological subtypes, tumor grades, menopausal status, and molecular alterations were compared. Results: Of the cases evaluated, 57 (70.4%) were endometrioid and 24 (29.6%) were serous carcinoma. TP53 variations were significantly higher in serous carcinomas compared to endometrioid tumors (66.7% vs. 26.3%; p = 0.001). In endometrioid carcinomas, the mean number of variants increased with advancing tumor grade (Grade 1: 4.44; Grade 2: 9.68; Grade 3: 11.42; p = 0.006). Alterations in BLM, CDC27, MLH3, and MSH3 were more frequently observed in high-grade tumors. In exploratory analyses, no significant differences were detected between the premenopausal and postmenopausal groups regarding total variant load, number of altered genes, MSI status, or the distribution of TCGA-inspired molecular subgroups; however, these comparisons were limited by the small number of premenopausal patients. The most frequent co-mutation was observed between BLM and CDC27 (55.6%). In the TCGA-inspired molecular classification, the most prevalent subgroup was NSMP-proxy (33.3%). Conclusions: Serous and endometrioid endometrial cancers display distinct molecular characteristics. In endometrioid carcinomas, the genomic alteration load increases in parallel with advancing tumor grade. TCGA-inspired molecular classification and co-mutation analyses revealed the prominent molecular heterogeneity of endometrial cancer. In exploratory analyses, no significant differences were detected between the premenopausal and postmenopausal groups regarding total variant load, number of altered genes, MSI status, or the distribution of TCGA-inspired molecular subgroups. However, these findings should be interpreted with caution because of the limited number of premenopausal patients. Given the limited number of premenopausal patients, findings related to menopausal status should be considered exploratory and require validation in larger, independent cohorts.