Akademik Veri Yönetim Sistemi
2nd International Hereditary Cancer Congress, Antalya, Türkiye, 5 - 08 Şubat 2026, ss.24, (Özet Bildiri)
Introduction: Familial Adenomatous Polyposis (FAP) is an autosomal dominant hereditary colorectal cancer syndrome caused by pathogenic germline variants in the APC gene. While sequence analysis identifies the majority of causative variants, a subset of patients harbor large genomic rearrangements that may be missed by standard next-generation sequencing (NGS) panels. This highlights the importance of complementary copy number variation (CNV) analysis in clinically suspected FAP cases with negative sequencing results. Case Presentation: We report the case of a 52-year-old female patient who underwent total colectomy in 2011 due to the presence of more than 100 tubular adenomas, consistent with a clinical diagnosis of FAP. The patient had no significant comorbidities and was not using any chronic medication. Family history was remarkable: two male siblings had been clinically diagnosed with FAP and died from colorectal cancer at the ages of 37 and 49, respectively. There was no reported history of FAP among distant relatives. Additional familial malignancies included thyroid cancer in a maternal aunt and lymphoma in a paternal aunt. Both parents had died suddenly at relatively young ages (54 and 57 years), with no documented cancer diagnosis. Methods-Results: To establish a molecular diagnosis, a hereditary cancer panel including 41 genes was initially performed using NGS technology. No pathogenic or likely pathogenic variants were detected by sequence analysis. Given the strong clinical suspicion of FAP, CNV analysis was subsequently performed, revealing a deletion encompassing exons 7–11 of the APC gene. To confirm this finding, multiplex ligation-dependent probe amplification (MLPA) analysis was requested. MLPA results demonstrated a heterozygous deletion involving APC exon 9 through intron 13 (rsA5q22.2), confirming the presence of a large genomic rearrangement. Conclusion: This case underscores the critical role of CNV analysis and MLPA in the molecular diagnosis of FAP, particularly in patients with strong clinical and familial evidence but negative initial NGS sequencing results. Comprehensive genetic testing strategies that include both sequence and dosage analyses are essential to avoid false-negative results, ensure accurate diagnosis, and enable appropriate genetic counseling and surveillance for affected families.