Genomic characterization of lymphomas in patients with inborn errors of immunity

Xiaofei Ye, Paul J. Maglione, Claudia Wehr, Xiaobo Li, Yating Wang, Hassan Abolhassani, Elena Deripapa, Dongbing Liu, Stephan Borte, Likun Du, Hui Wan, Andreas Plötner, Yvonne Giannoula, Huai Bin Ko, Yong Hou, Shida Zhu, Jennifer K. Grossman, Birgitta Sander, Bodo Grimbacher, Lennart HammarströmAlina Fedorova, Sergio D. Rosenzweig, Anna Shcherbina, Kui Wu, Klaus Warnatz, Charlotte Cunningham-Rundles, Qiang Pan-Hammarström

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


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 8 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 d syndrome patients. We also identified 5 genomic mutational signatures, including 2 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.

Original languageEnglish
Pages (from-to)5403-5414
Number of pages12
JournalBlood advances
Issue number18
StatePublished - 27 Sep 2022


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