Akademik Veri Yönetim Sistemi
2nd International Hereditary Cancer Congress, Antalya, Türkiye, 5 - 08 Şubat 2026, ss.42, (Özet Bildiri)
Introduction: PALB2 (Partner and Localizer of BRCA2) is a critical gene in the homologous recombination DNA repair pathway, and its role in hereditary cancer predisposition is increasingly recognized. Germline pathogenic or likely pathogenic variants (PV/LPV) in PALB2 lead to genomic instability and are associated with an increased risk of breast, pancreatic, and ovarian cancers. The reported frequency of pathogenic PALB2 variants in hereditary cancer cohorts ranges from 0.4% to 1.2%. This study aimed to evaluate the frequency and clinical characteristics of PALB2 variants detected in individuals undergoing hereditary cancer panel testing. Methods: A total of 635 individuals who presented to the Department of Medical Genetics at Dokuz Eylül University between 2024 and 2025 were retrospectively analyzed. All participants had a personal and/or family history of cancer and underwent multigene hereditary cancer panel testing. Identified PALB2 variants were classified according to the American College of Medical Genetics and Genomics (ACMG) criteria. Results: PV/LPVs in PALB2 were identified in 3 of 635 individuals (0.47%). Among these, one patient had breast cancer, one had ovarian cancer, and one had a gastrointestinal stromal tumor (GIST). All three carriers had a positive family history of cancer. Variants of uncertain significance (VUS) were detected in 11 individuals (1.7%), including one novel variant. The VUS group consisted of 10 females and one male, with breast cancer being the most common indication for testing. No biallelic pathogenic variants were identified. Discussion: Existing literature indicates that PALB2-associated breast cancers frequently display invasive ductal carcinoma histology, high tumor grade, and HER2-negative status. While hormone receptor positivity is common, the prevalence of triple-negative breast cancer is higher than in the general population. In our cohort, one breast cancer patient carried the pathogenic c.1684+2T>G variant, presenting with invasive ductal carcinoma, which is consistent with previous reports. The ovarian cancer patient carried the pathogenic c.932_933insC variant and had a first-degree relative with breast cancer. Although the lifetime risk of ovarian cancer is lower than that of breast cancer in PALB2 carriers, these cases are typically high-grade serous carcinomas. Our findings align with these clinical characteristics. Notably, one patient with a pathogenic variant was diagnosed with GIST. As PALB2 is not currently an established predisposition gene for GIST, this may represent a sporadic occurrence. However, given the patient’s family history of breast cancer, segregation analysis is planned to further clarify the association. The VUS detection rate was 1.7%. Nine of these carriers had breast cancer, while one presented with co-existing renal cell carcinoma and lung cancer. All VUS carriers are undergoing genetic counseling, with variant re evaluation planned as new evidence emerges. Emerging data suggests that PALB2-associated cancers may show increased sensitivity to platinum-based chemotherapy and PARP inhibitors due to homologous recombination deficiency. Therefore, identifying PALB2 variants is vital for both surveillance and personalized treatment selection. Conclusion: The detection of PALB2 variants is clinically significant for risk assessment, cascade testing in families, and therapeutic decision-making. The VUS rate underscores the ongoing need for population-specific data and functional studies to improve variant interpretation.