Molecular and pathological characterisation of diffuse large B-cell lymphomas in children with Nijmegen breakage syndrome

Nijmegen-breakage syndrome (NBS, OMIM #251260) is an autosomal recessive chromosomal instability syndrome characterized by a very distinct phenotype (microcephaly, growth retardation, immunodeficiency) associated with increased predisposition to develop malignancies, particularly of lymphoid origin (by the age of 20 years, over 40% of NBS patients develop cancer). Immunological lineage of lymphomas in NBS significantly differs from Non-Hodgkin Lymphomas (NHL) entities observed in general pediatric population as well as in primary immunodeficiencies. There is a strong predominance of diffuse large B-cell lymphoma (DLBCL) and T cell lymphoblastic lymphoma (T-LBL/ALL), all showing clonal Ig/TCR rearrangements. In the current study we aimed to examined gene expression signature of metabolic pathways in DLBCL cells. Overall design: Comparative gene expression profiling analysis of RNA-seq data for 41 human FFPE samples, of which 8 had confirmed Nijmegen breakage syndrome and 22 presented immunohistochemistry-confirmed Germinal center B-cell like sub-type of diffuse large B-cell lymphoma