Germline Cancer Predisposition in Pediatric Solid Tumors
2nd International Hereditary Cancers Congress, Antalya, Türkiye, 5 - 08 Şubat 2026, ss.29, (Özet Bildiri)
- Yayın Türü: Bildiri / Özet Bildiri
- Basıldığı Şehir: Antalya
- Basıldığı Ülke: Türkiye
- Sayfa Sayıları: ss.29
- İstanbul Üniversitesi Adresli: Evet
Özet
Objective: Solid tumors constitute a heterogeneous group of malignancies arising from non-hematopoietic tissues, and represent a substantial proportion of childhood cancers. Although pediatric cancers are rare and represent approximately 1-2% of all malignancies, solid tumors constitute nearly 40-50% of childhood cancer cases. Increasing evidence indicates that a approximately 8-12% of unselected pediatric cancer patients harbor pathogenic/likely pathogenic (P/LP) germline variants in cancer predisposition genes. This study aimed to evaluate the contribution of germline cancer predisposition to pediatric solid tumors using clinical exome sequencing (CES) in children and adolescents aged 0-18 years. Germline variants in cancer predisposition genes were systematically analyzed to determine the frequency and molecular spectrum of P/LP variants and to assess their potential clinical relevance for patient management, surveillance, and genetic counseling. Materials-Methods: A total of 56 pediatric patients diagnosed with solid tumors were included in the study, encompassing a broad spectrum of tumor types, including central nervous system tumors, sarcomas, renal tumors, and other extracranial solid malignancies. Germline analysis was performed using CES on DNA extracted from peripheral blood samples, targeting more than 100 cancer predisposition genes. Rare variants with a minor allele frequency <=0.1% classified as pathogenic, likely pathogenic, or variants of uncertain significance were evaluated, and copy number variation analysis was performed across all genes included in the panel. Identified candidate variants were assessed together with parental segregation analysis. Results: The cohort included 56 patients with solid tumors, classified as central nervous system tumors (n=18, 32.1%), soft tissue and bone tumors (n=17, 30.4%), renal tumors (n=8, 14.3%), and other solid tumors (n=13, 23.2%). At the time of submission, CES analysis was completed in 26 patients, while analyses in 30 patients were ongoing. Among patients with completed analysis, P/LP germline variants were identified in 11 patients (42.3%). The most frequently affected gene was NF1 (n=7), and all NF1 patients were diagnosed with central nervous system tumors, especially gliomas. Additional P/LP variants were detected in RB1 (retinoblastoma, n=2), PTEN (glioma, n=1), DICER1 (ovarian Sertoli-Leydig cell tumor, n=1), RET (atypical bronchial carcinoid tumor, n=1), and TSC2 (glioma and cardiac rhabdomyoma, n=1). Conclusion: Germline cancer predisposition in pediatric solid tumors remains underexplored despite its potential impact on diagnosis, management, and surveillance. In this study, the identification of P/LP germline variants in a notable subset of children with solid tumors reinforces the relevance of systematic germline evaluation in pediatric cancers. The higher detection rates observed in this cohort likely reflect the inclusion of clinically selected patients, underscoring the importance of heightened awareness in the presence of clinical red flags such as early-onset disease, specific tumor types, or suggestive family histories. These findings emphasize that germline analyses should be considered an integral component of the diagnostic workup in pediatric cancer patients. Completion of the ongoing analyses is expected to further clarify the spectrum and frequency of germline predisposition, and the full results will be presented at the time of the conference presentation. Keywords: clinical exome sequencing, germline cancer predisposition, pediatric solid tumors