Menopausal status affects the prognoses and consequences of breast cancer. Therefore, this retrospective study aimed to reveal the molecular variation profile differences in breast cancer patients according to their menopausal status, with the hypothesis that the molecular variation profiles will be different at premenopausal and postmenopausal ages. Breast cancer patients (n = 254) who underwent molecular subtyping and QIAseq Human Breast Cancer NGS Panel screening between 2018 and 2022 were evaluated retrospectively. Their menopausal status was defined by age, and those aged 50 years and above were considered postmenopausal. Of the subjects, 58.66% (n = 149) were premenopausal and 41.34% (n = 105) were postmenopausal. The mean age at the time of diagnosis for all patients was 49.31 ± 11.19 years, with respective values of 42.11 ± 5.51 and 59.54 ± 9.01 years for the premenopausal and postmenopausal groups, respectively (p = 0.000). Among premenopausal patients, the percentages of patients in BCa subtypes (luminal A, luminal B-HER2(−), luminal B-HER2(+), HER2 positive, and triple-negative) were determined to be 34.90%, 8.05%, 26.17%, 10.74%, and 20.13%, respectively, while in the postmenopausal group, these values were 39.05%, 16.19%, 24.76%, 6.67%, and 13.33%, respectively (p > 0.05). Considering menopausal status, the distribution of hormone receptors in premenopausal patients was ER(+)/PgR(+) 63.76%, ER(−)/PgR(−) 23.49%, ER(+)/PgR(−) 10.74%, and ER(−)/PgR(+) 2.01%, respectively, while in postmenopausal women, this distribution was observed to be 74.29%, 23.81%, 1.90% and 0.00% in the same order (p = 0.008). The most frequently mutated gene was TP53 in 130 patients (51.18%), followed by PIK3CA in 85 patients (33.46%), BRCA2 and NF1 in 56 patients (22.05%), PTEN in 54 patients (21.26%), and ATR and CHEK2 in 53 patients (20.87%). TP53, PIK3CA, NF1, BRCA2, PTEN, and CHEK2 mutations were more frequently observed in premenopausal patients, while TP53, PIK3CA, BRCA2, BRCA1, and ATR mutations in postmenopausal patients. These findings contribute to a deeper understanding of the underlying causes of breast cancer with respect to menopausal status. This study is the first from Turkey that reflects the molecular subtyping and somatic mutation profiles of breast cancer patients according to menopausal status.

Background: Understanding PIK3CA mutations and co-mutations in non-small cell lung carcinoma (NSCLC) is critical to developing personalized treatment strategies. Therefore, this study aims to investigate PIK3CA mutations and the accompanying somatic variations in NSCLC. Methods: This retrospective study included 98 patients over 18 years of age who were diagnosed with NSCLC, operated on, and referred to the Molecular Pathology Laboratory between January 2019 and June 2024 for next-generation sequencing panel tests and ALK-ROS1 FISH analysis. Results: All patients were found to carry PIK3CA mutations. Among the 98 NSCLC patients analyzed, 16 (16.33%) were female and 82 (83.67%) were male. The average age of the patients was 64.53 ± 9.63 years, with an age range of 38–84 years, and the majority were 50 years or older. Of the cases, 51 presented the adenocarcinoma subtype, while the remaining 47 showed the squamous cell carcinoma subtype. A smoking history was present in 77 (78.57%) patients, while 21 (21.43%) had no smoking history. The most frequently detected pathogenic or likely pathogenic PIK3CA variations were c.1633G>A p.E545K (32.65%), c.1624G>A p.E542K (11.22%), c.3140A>G p.H1047R (11.22%), c.3140A>T p.H1047L (5.10%), c.1357G>C p.E453Q (4.08%), and c.3143A>G p.H1048R (2.04%). The top 10 mutations that most commonly accompanied PIK3CA variations were KRAS, NF1, TP53, EGFR, PTEN, BRAF, KIT, CDKN2A, SMARCA4, and ATM mutations, respectively. Conclusions: PIK3CA variations, along with other gene variations, may influence cancer progression and thus may play a crucial role in the determination of targeted treatment strategies.

Introduction: Absence of mismatch repair (MMR) genes in tumor cells or errors in the replication repair process may lead to DNA-MMR deficiency and microsatellite instability (MSI) formation. Specific tumor environments where gene variations are observed are believed to be conducive to the formation of MSI. This study aimed to determine the MSI status, MMR protein expression, and somatic mutation profile in solid organ tumors.Material and methods: In this study, the records of 192 patients with solid organ tumors who were referred to the Molecular Pathology Laboratory between January 2018 and December 2022 were reviewed retrospectively. The MSI profiles of the patients were evaluated using real-time polymerase chain reaction (PCR) and immunohistochemical (IHC) methods. Somatic variations in the patients were detected using an NGS colon cancer panel.Results: In the IHC evaluation, 22 cases showed MMR-deficient (dMMR) or high MSI (MSI-H), and 170 cases showed MMR-proficient (pMMR) or microsatellite stable (MSS). Real-time PCR results on the 22 dMMR cases revealed that 11 cases had MSI-H and 11 cases had MSS status. Among the 170 cases with pMMR, 160 cases were found to have MSS status, while 10 cases had low MSI (MSI-L). NGS analysis revealed that the three most frequent pathogenic variants in all cases were BLM exon 7 c.1544delA, MSH3 exon 7 c.1148delA, and MLH3 exon 2 c.1755delA. MSI-H cancer patients had a higher variation burden compared to MSS cancer patients. The most frequently observed pathogenic variant in both MSI-H and MSS cancer patients was BLM exon 7 c.1544delA.Conclusions: Our study covers not only colorectal cancer patients but also other solid tumor types, providing the first data from the Turkish population on the MSI-H/dMMR status and somatic mutation profile in the presence of this condition.

Chronic lymphocytic leukemia (CLL) is a hematological disease characterized by the proliferation of monoclonal B-lymphocytes. Although autoimmune complications such as autoimmune hemolytic anemia and immune thrombocytopenia are common in CLL patients, nonhematological autoimmune complications are rather rare. The most common renal involvements are membranoproliferative glomerulonephritis and minimal change disease. Focal segmental glomerulosclerosis (FSGS) is predominantly associated with Hodgkin's lymphoma among hematological malignancies. FSGS associated with CLL is rarely reported in the literature, with a poor understanding of the common pathophysiology and a very limited experience with this co-occurrence. Although Rai Stage 1/Binet Stage B CLL, our 61-year-old case, who was diagnosed with secondary FSGS, which is a very rare complication, was treated with fludarabine, cyclophosphamide, and rituximab (FCR) combination. Following the treatment, a complete response was achieved about CLL, and the patient, whose renal findings recovered, is in remission and under follow-up for six years. Although the mechanisms between CLL and autoimmune complications are not fully elucidated, it is usually related to immune disorders like an abnormal T-cell response and polyclonal antibody production. While FSGS is very rare in lymphoma, its co-existence with CLL is reported only in a limited number of case reports. Steroids may be used in these patients; however, in cases not responding to steroids, treatment of the underlying CLL is required.

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.

Homologous recombination deficiency (HRD) is a critical indicator of genomic instability; however, the composite HRD score may not reflect the distribution of distinct genomic scar components underlying this phenotype. In this exploratory study, we compared the absolute and relative contributions of loss of heterozygosity (LOH), large-scale state transitions (LST), and telomeric allelic imbalance (TAI) among solid tumors harboring pathogenic or likely pathogenic (P/LP) variants in BRCA1 or BRCA2. This retrospective study included 76 patients with solid tumors who underwent HRD testing between January 2023 and January 2026. P/LP variants in homologous recombination repair (HRR) genes, alongside LOH, LST, and TAI scores, were evaluated. The composite HRD score was calculated as LOH + LST + TAI, with values ≥ 56 defined as HRD-positive. Additionally, the relative contribution of each scar component to the total HRD score was determined. Given the small sizes of the BRCA1-only and BRCA2-only subgroups and the heterogeneity of the overall cohort, all gene-group comparisons were considered exploratory and hypothesis-generating. Overall, 21.1% of the cohort was HRD-positive. Patients harboring BRCA1/2 P/LP variants displayed a significantly higher median HRD score compared to non-carriers (47.0 vs. 30.0; p = 0.016). When comparing patients with tumors harboring BRCA1-only (n = 9) and BRCA2-only (n = 10) P/LP variants, LOH was higher in the BRCA2 group (19.0 vs. 5.0; p = 0.036); however, this difference did not retain statistical significance following false discovery rate (FDR) adjustment (q = 0.108). In an exploratory sensitivity analysis restricted to breast and ovarian tumors (BRCA1-only, n = 5; BRCA2-only, n = 9), the LOH/HRD ratio was higher in the BRCA2 group (0.301 vs. 0.000; p = 0.026; q = 0.039), whereas the LST/HRD ratio was higher in the BRCA1 group (0.488 vs. 0.310; p = 0.019; q = 0.039). These estimates were based on very small subgroups and should therefore be interpreted cautiously. This exploratory analysis identified differences in the relative distributions of LOH and LST between tumors harboring BRCA1-only and BRCA2-only P/LP variants, particularly in the breast/ovarian subset. However, the small and heterogeneous subgroups, together with the absence of systematic assessment of biallelic BRCA1/2 inactivation, preclude gene-specific or mechanistic conclusions. These observations should be regarded as hypothesis-generating and require validation in larger, tumor-specific, independent cohorts.