The mutational signature of chronic lymphocytic leukemia

Advances in next-generation sequencing technologies continue to unravel the cancer genome, identifying key biological pathways important for disease pathogenesis and clinically relevant genetic lesions. These studies have provided unprecedented resolution of the cancer genome, facilitating significant advances in the ability to detect many cancers, and predict patients who will develop an aggressive disease or respond poorly to treatment. The mature B-cell neoplasm chronic lymphocytic leukaemia remains at the forefront of these genomic analyses, largely due its protracted natural history and the accessibility to suitable material for study. We now possess a comprehensive view of the genomic copy number mutational landscape of the disease, as well as a detail description of clonal evolution, and the molecular mechanisms that drive the acquisition of genomic lesions and more broadly, genomic complexity. Here, recent genomic insights with associated biological and clinical implications will be reviewed.