3D genome dynamics in normal and neoplastic B cells
Knowledge of one-dimensional changes in the genome, such as mutations and changes in DNA methylation, has had a huge impact on our understanding and the clinical management of hematological malignancies. “However, the two meters of DNA in each cell make up a three-dimensional (3D) network”, explained Dr Iñaki Martin-Subero (University of Barcelona, Spain) in the Late Breaking oral session. Using a technique called in situ HiC-seq, he and his group were able to map 3D chromatin interactions and discern active and inactive compartments.
In total, they analyzed 10 different ‘omics’ layers per sample, including gene expression and DNA methylation, in normal B lymphocytes, representing different stages of differentiation, and in neoplastic B cells from CLL and mantle cell lymphoma (MCL). “All these 10 layers have been analyzed in the same samples”, Martin-Subero stressed.
Bioinformatic analysis of the data showed that the 3D genome structure changes during B cell differentiation and is maturation stage specific. The investigators observed altered 3D genome structures in neoplastic B cells, and CLL samples had more alterations than MCL samples. In these samples, DNA blocks that became active or inactive contained genes related to disease pathogenesis.