Genetic heterogeneity in childhood leukemia/lymphoma: a Turkish cohort with strong predisposition


ÖNDER G., ÖZDEMİR Ö., Taylan F., CANPOLAT C., Yalcin K., Erbey F., ...Daha Fazla

Frontiers in Genetics, cilt.16, 2025 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 16
  • Basım Tarihi: 2025
  • Doi Numarası: 10.3389/fgene.2025.1624306
  • Dergi Adı: Frontiers in Genetics
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, EMBASE, Veterinary Science Database, Directory of Open Access Journals
  • Anahtar Kelimeler: cancer predisposition, childhood leukemia, childhood lymphoma, germline variants, short-read sequencing
  • Acıbadem Mehmet Ali Aydınlar Üniversitesi Adresli: Evet

Özet

Background: Leukemia is the most common cancer in children, and 10%–15% of patients with leukemia/lymphoma carry pathogenic germline cancer-predisposing variants. Identifying these variants is critical for understanding the genetic predisposition and optimizing clinical management. Methods: We performed germline short-read sequencing in 36 individuals from 20 families with suspected leukemia/lymphoma predisposition, including 20 index cases, 9 affected relatives, and 7 unaffected members. Results: We identified 13 clinically relevant germline variants in known cancer predisposition genes including TP53, ETV6, MSH6, MLH1, and BRCA1. Notably, we uncovered novel candidate variants in ATR, TNFRSF9, ETAA1, and KSR1, which was supported by segregation analysis, consanguinity patterns, and secondary malignancy phenotypes. Several index cases exhibited striking familial cancer syndromes involving both hematologic and solid tumors, with progression from ALL to AML or glioma. Deep clinical–genomic correlation enabled reclassification of variants and refined diagnostic and therapeutic decision-making in multiple cases. The patients were referred to genetic counseling for surveillance of carriers and risk assessment for various family members. Conclusion: These findings emphasize the clinical utility of germline testing in pediatric hematologic cancers by providing novel insights into the predisposition to leukemia/lymphoma and contributing to treatment regimens, donor selection, and diagnostic refinement, particularly in populations with high consanguinity.