Research interests Our research group is interested in the analysis of the genome and epigenome of mature B-cell tumours. Over three billion base-pairs of deoxyribonucleic acid (DNA), bound with accessory proteins in the form of chromatin, are super-coiled and packed into 23 autosomal and sex-determining chromosomes, constituting the human genome, the genetic blueprint for normal human development and cellular function. A leukaemic cell, in addition to carrying this diploid genome that has been inherited from both parents, has also acquired a series of somatic genomic lesions, including base-pair mutations, chromosomal rearrangements and large-scale copy number alterations (CNAs). Epigenetic defects in the form of disordered DNA methylation, chromatin remodelling and dysregulation of small noncoding micro-ribonucleic acids (miRNAs) are also present. The acquisition of these (epi)genomic defects can enable many of the hallmarks of leukaemogenesis, such as the promotion of proliferative signalling, the evasion of growth suppression and the resistance to apoptosis. Our work has involved the identification and characterisation of these defects, and these insights have helped us understand the leukaemic process, improving cancer diagnosis, accurate risk-adapted stratification and the development of targeted treatments for precision medicine. Our laboratory works on a number of B-cell tumours, principally chronic lymphocytic leukaemia (CLL) and splenic marginal zone lymphoma (SMZL), and to a lesser extent follicular (FL) and diffuse large b-cell lymphoma (DLBCL). CLL is the most common form of leukaemia in Western populations, accounting for approximately one-third of all new diagnoses. Clinically, the disease is highly heterogeneous, with patients surviving for decades with a benign disease requiring no treatment, while others exhibit a rapidly progressive disease despite aggressive therapy. SMZL is considered a low grade, indolent B-cell neoplasm with a median survival of approximately 10 years, but 70% of patients present with or develop progressive disease with a requirement for therapy, and 5–10% will undergo transformation to a large B-cell lymphoma. For both diseases, no biomarkers accurately predict the disease course, particularly in early stage disease. Furthermore, definitive diagnosis of SMZL can be challenging. In CLL, we have identified, or help characterize many of the recurrently mutated genes emerging from recent high-throughput sequencing studies. We continue to be at the centre of large international collaborative studies, mapping the CLL genome and assessing the clinical importance of gene mutations. In SMZL, we published one of the seminal studies identifying KLF2 as a target of novel recurrent gene mutations. We currently lead a large international study investigating the importance of somatic mutations and DNA methylation changes in SMZL.