The Mutation of CD27 Deficiency Presented With Familial Hodgkin Lymphoma and a Review of the Literature
Doğan Köse1, Ahmet Güzelçiçek2, Özlem Öz3
1Departments of Pediatric Hematology and Oncology.
Insights
This study links CD27 deficiency to Hodgkin lymphoma risk in siblings. Homozygous CD27 variants were found in affected children, suggesting a genetic link, but environmental factors may also play a role.
Area of Science:
- Immunology
- Genetics
- Oncology
Background:
- CD27 is a crucial protein in the immune system, involved in lymphocyte activation and differentiation.
- Hodgkin lymphoma is a cancer of the lymphatic system with complex etiology.
- Genetic predispositions are increasingly recognized in various cancers, including lymphomas.
Observation:
- A family with a high incidence of Hodgkin lymphoma was investigated for CD27 mutations.
- Exome sequencing identified a shared heterozygous CD27 variant in the parents and a homozygous variant in affected siblings.
- The study observed that CD27 deficiency might influence regulatory T cell (Treg) differentiation.
Findings:
- Four siblings with Hodgkin lymphoma were homozygous for a specific CD27 variant.
- Other homozygous siblings without lymphoma suggest additional contributing factors.
- The genetic analysis confirmed a strong association between CD27 deficiency and Hodgkin lymphoma susceptibility.
Implications:
- This research strengthens the evidence for CD27 mutations as a significant factor in Hodgkin lymphoma etiology.
- The findings highlight the potential role of genetic screening for CD27 deficiency in at-risk families.
- Environmental factors likely interact with genetic predisposition in the development of Hodgkin lymphoma.
Abstract:
This study aimed to report 4 siblings with CD27 deficiency presented with Hodgkin lymphoma. The father of the family, his 2 wives, and 17 children born from these wives were included into the study. CD27 mutation of all the family members with, and without Hodgkin lymphoma were studied. The variants detected by the exome sequencing analysis were verified by Sanger sequencing and analyzed using SeqScape Software 3. It was determined that both the father of the family and his 2 wives carried the same variant heterozygously. Of the children born to the first mother, 2 children were normal, 3 were heterozygous and 5 were homozygous. Four of these 5 homozygous children were diagnosed with Hodgkin lymphoma. Of the children born to the second mother, 1 child was normal, 3 children were heterozygous and 2 children were homozygous, and none of them had developed a malignant event. We also showed that CD27 deficiency may enhance Treg differentiation. According to our information, this study augmented the relationship of Hodgkin lymphoma and CD27 deficiency. The detection of homozygous CD27 variant in all siblings who developed lymphoma strengthened the place of this mutation in the etiology of Hodgkin lymphoma. In contrast, the presence of homozygous siblings with no malignant event suggested the possible contributions of environmental factors on the etiology.
