Genetic heterogeneity in childhood leukemia/lymphoma: a Turkish cohort with strong predisposition
Year: 2025
Type: article
Study design: Observational Study
Abstract: 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: , 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.
Source: Frontiers in Genetics
Authors: Gizem Onder, Ozkan Ozdemir, Fulya Taylan, Cengiz Canpolat, Koray Yalcin, Fatih Erbey, Banu Oflaz Sozmen, Fikret Asarcikli, Turan Bayhan, Yunus Murat Akcabelen, Nese Yarali, Namik Yasar Ozbek, Ikbal Ok Bozkaya, Dilek Kacar, Berk Ergun, Alper Akkus, Davut Albayrak, Elif Ince, Ugur Demirsoy, Gul Nihal Ozdemir, Omer Dogru, Seda Aras, Eylul Aydin, Busra Unal, Ufuk Amanvermez, Ozlem Akgun Dogan, Sezer Akyoney, Muge Sayitoglu, Ann Nordgren, Nihat Bugra Agaoglu, Ugur Ozbek, Ozden Hatirnaz Ng
Institutions: Karolinska Institutet, Acıbadem University, Karolinska University Hospital, Bahçeşehir University, Koç University, Ankara Yıldırım Beyazıt University, Ankara Bilkent City Hospital, Ankara University, Kocaeli Üniversitesi, Istinye University, Biruni University, Ümraniye Eğitim ve Araştırma Hastanesi, Istanbul University, Sahlgrenska University Hospital, University of Gothenburg, Krankenhaus Nordwest, Dokuz Eylül University
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
Awards: G2030989679, G910680712
OpenAlex ID: W4414148565