Genomic characterization of lymphomas in patients with inborn errors of immunity

Patients with inborn errors of immunity (IEI) have a higher risk developing cancer, especially lymphoma. However, the molecular basis for IEI-related lymphoma is complex and remains elusive. Here, we perform an in-depth analysis genomes derived from 23 IEI patients. We identified validated disease-causing or associated germline mutations in 14 patients involving ATM, BACH2, BLM, CD70, G6PD, NBN, PIK3CD, PTEN, TNFRSF13B. Furthermore, profiled somatic genome eight genes that were mutated at significantly level IEI-associated diffuse large B-cell lymphomas (DLBCLs) than non-IEI DLBCLs, such as BRCA2, NCOR1, KLF2, FAS, CCND3, BRWD3. The latter, BRWD3, furthermore preferentially tumors subgroup activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) also five genomic mutational signatures, including two DNA repair deficiency-related strikingly high number inter- intrachromosomal structural variants tumor Bloom patient. In summary, our comprehensive characterization rare genetic disorders expands understanding lymphomagenesis provides new insights targeted therapy. research was funded by: Swedish Cancer Society (Cancerfonden), Research Council, Childhood fund, NSFC (81670184), Radiumhemmet CIMED, Knut Alice Wallenberg Foundation Keywords: Aggressive non-Hodgkin lymphoma, Genomics, Epigenomics, Other -Omics, Tumor Biology Heterogeneity No conflicts interests pertinent to abstract.