Broadening the Clinical and Molecular Spectrum of BAP1 Tumor Predisposition Syndrome: Findings from the First Reported Turkish Cohort

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DURMAZ ÖZDİNÇ C. D., Taşdelen E., KINDIŞ E., Baltacı H. N. C., KOÇ İ., Bulut N. S., ...Daha Fazla

Acta Haematologica Oncologica Turcica, cilt.58, sa.3, ss.232-239, 2025 (Scopus, TRDizin)

Özet

Aim: BAP1-tumor predisposition syndrome (BAP1-TPDS) is a rare autosomal dominant condition predisposing to multiple malignancies, most notably uveal melanoma and mesothelioma. The full phenotypic and genotypic spectrum remains incompletely defined, particularly in underrepresented populations. Methods: Six unrelated Turkish probands carrying germline pathogenic or likely pathogenic BAP1 variants were identified through multigene hereditary cancer panel testing. Clinical data, family histories, and segregation analyses were evaluated, and variant classification followed American College of Medical Genetics and Genomics guidelines. Results: All six affected individuals were female, with cancer onset between 38 and 57 years of age. Breast carcinoma was the most common diagnosis (n=4), followed by uveal melanoma (n=2). Three novel BAP1 variants were identified, expanding the mutational landscape of BAP1-TPDS. Pedigree analysis revealed extensive familial clustering of malignancies, including uveal melanoma, colon carcinoma, hepatocellular carcinoma, and mesothelioma. None of the breast cancer patients carried additional pathogenic variants in known susceptibility genes. Conclusion: This study describes the first Turkish cohort of germline BAP1 carriers and broadens the clinical and genetic spectrum of BAP1-TPDS. The predominance of breast carcinoma highlights the need to consider BAP1 testing in patients with early-onset or familial breast cancer. Integrating BAP1 analysis into hereditary cancer panels will enhance recognition, risk stratification, and surveillance across diverse populations.