Genome-wide sequencing studies in pediatric cancer cohorts indicate that about 10% of patients have germline mutations within cancer predisposition genes. Within this group, primary immune deficiencies take the priority regarding the vulnerability of the patients to infectious agents and the difficulties of cancer management. On the other hand, early recognition of these diseases may offer specific targeted therapies and hematopoietic stem cell transplantation as an option. Besides therapeutic benefits, early diagnosis will provide genetic counseling for the family members. Within this context, an extended family with multiple consanguineous marriages and affected individuals, who presented with combined immune deficiency (CID) and/or Hodgkin lymphoma phenotype, were examined by exome sequencing. A pathogenic homozygous missense CD70 variation was detected (NM_001252.5:c332C>T) in concordance with CD70 phenotype and familial segregation was confirmed. CD70 variations in patients with CID and malignancy have very rarely been reported. This paper reports extended family with multiple affected members with CID and malignancy carrying a missense CD70 variation, and reviews the rare cases reported in the literature. Primary immune deficiencies appear to be a potential cause for pediatric cancers. Better focusing on these inborn disorders to prevent or make an early diagnosis of malignant transformation and reduce mortalities is important.
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This project is supported by Istanbul University Research Fund with the project number: TOA 20499 and by Bilgi University Research Fund: 2018.01.006. The authors thank Prof Emin Darendeliler, Dr. Ayca Iribas, Istanbul University, Oncology Institute, Department of Radiation Oncology; Assoc. Prof Muge Gokce, Bahcelievler Memorial Hospital and The Stem Cell Transplantation Unit of the Medicalpark, Bahcelievler Hospital for the support in the treatment of the patients; and Emine Hafize Erdeniz from Erzurum Education and Research Hospital for providing patient information.
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Khodzhaev, K., Bay, S.B., Kebudi, R. et al. Lymphoma Predisposing Gene in an Extended Family: CD70 Signaling Defect. J Clin Immunol 40, 883–892 (2020). https://doi.org/10.1007/s10875-020-00816-4
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