Structural genomic alterations in primary mediastinal large B-cell lymphoma

Leuk Lymphoma. 2015;56(8):2239-50. doi: 10.3109/10428194.2014.985673. Epub 2015 Jan 21.


Primary mediastinal large B-cell lymphoma (PMBCL) is an aggressive non-Hodgkin lymphoma that displays phenotypic and genotypic similarity to Hodgkin lymphoma and diffuse large B-cell lymphoma. Studies using genome-wide discovery tools have revealed specific, recurrent structural aberrations as critical somatic events in the pathogenesis of PMBCL. These structural alterations prominently include transcript and protein altering rearrangements and copy number variations of the programmed death ligands 1 (CD274) and 2 (PDCD1LG2), CIITA, JAK2 and REL. Importantly, evidence is emerging that these acquired structural genomic changes, in synergy with other somatic alterations, contribute to PMBCL pathogenesis by influencing tumor microenvironment interactions that favor malignant B-cell growth. The means by which these rearrangements arise are not well understood. However, analysis of breakpoint junctions at base-pair resolution provides preliminary insight into putative rearrangement mechanisms. As the field also anticipates predictive value and therapeutic targeting of structural changes involving programmed death ligands and JAK2, a review of therapies that will likely shape future lymphoma treatment is needed.

Keywords: CD274; CIITA; JAK2; PDCD1LG2; Primary mediastinal large B-cell lymphoma (PMBCL); REL; amplifications; fluorescence in situ hybridization (FISH); high-throughput sequencing; non-Hodgkin lymphoma (NHL); programmed death ligands; translocations.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Chromosome Aberrations
  • Genetic Variation*
  • Genome, Human*
  • Genomics*
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Lymphoma, Large B-Cell, Diffuse / metabolism
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Lymphoma, Large B-Cell, Diffuse / therapy
  • Mediastinal Neoplasms / genetics
  • Mediastinal Neoplasms / metabolism
  • Mediastinal Neoplasms / pathology
  • Mediastinal Neoplasms / therapy
  • Molecular Targeted Therapy
  • Mutation