Genomic characterization of lymphomas in patients with inborn errors of immunity
Abstract: Patients with inborn errors of immunity (IEI) have a higher risk of developing cancer, especially lymphoma. However, the molecular basis for IEI-related lymphoma is complex and remains elusive. Here, we perform an in-depth analysis of lymphoma genomes derived from 23 IEI patients. We identified and validated disease-causing or associated germline mutations in 14 of 23 patients involving ATM, BACH2, BLM, CD70, G6PD, NBN, PIK3CD, PTEN, and TNFRSF13B. Furthermore, we profiled somatic mutations in the lymphoma genome and identified eight genes that were mutated at a significantly higher level in IEI-associated diffuse large B-cell lymphomas (DLBCLs) than in non-IEI DLBCLs, such as BRCA2, NCOR1, KLF2, FAS, CCND3, and BRWD3. The latter, BRWD3, is furthermore preferentially mutated in tumors of a subgroup of activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome patients. We also identified five genomic mutational signatures, including two DNA repair deficiency-related signatures, in IEI-associated lymphomas and a strikingly high number of inter- and intrachromosomal structural variants in the tumor genome of a Bloom syndrome patient. In summary, our comprehensive genomic characterization of lymphomas derived from patients with rare genetic disorders expands our understanding of lymphomagenesis and provides new insights for targeted therapy
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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Blood advances. - 6, 18 (2022) , 5403-5414, ISSN: 2473-9537
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
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Universität
- (when)
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2022
- Creator
- DOI
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10.1182/bloodadvances.2021006654
- URN
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urn:nbn:de:bsz:25-freidok-2278578
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:36 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Ye, Xiaofei
- Wehr, Claudia
- Grimbacher, Bodo
- Warnatz, Klaus
- Pan-Hammarström, Qiang
- Universität
Time of origin
- 2022
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