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High-grade B-cell lymphoma with  MYC  and  BCL2  and/or  BCL6  rearrangements (DH/TH-HGBL) still miss an in-depth genomic characterization. To identify accompanying genetic events, we performed a pilot study on 7 cases by applying DNA microarray and targeted NGS sequencing. Interestingly, the genetic background of DH/TH-HGBL is largely overlapping with that of other high-grade/poor prognosis lymphomas. Namely, copy number abnormalities were trisomy of chromosome 7 and chromosome 8q gain, encompassing  MYC . Among gene variants, those affecting transcription factors ( MYC, FOXO1 ), epigenetic modulators ( KMT2D ,  EZH2  and  CREEBP ), and anti-apoptotic gene ( BCL2 ), were recurrent.  MYC  and  BCL2  were mutated in 3 and 5 cases, respectively. In addition, mutations of  FOXO1,  previously reported in Diffuse Large B-Cell Lymphomas, were also detected. Clarifying the genomic background of this subset of high-risk lymphomas will pave the way for the clinical use of new biomarkers to: (1) monitor treatment response and; (2) consider alternative targeted therapies.

leukemia and lymphoma

High grade B-cell lymphoma with  MYC ,  BCL2  and/or  BCL6  rearrangements: unraveling the genetic landscape of a rare aggressive subtype of non-Hodgkin lymphoma