Detection of clinically relevant molecular alterations in CLL by nanopore sequencing
About Adam Burns
Dr Adam Burns is a post-doctoral researcher in the Oxford Molecular Diagnostics Centre based in the Department of Oncology at the University of Oxford. His research focuses on developing next-generation sequencing-based tools for clinical diagnostic use. After obtaining his BSc from the University of Hull, Adam worked in industry for five years before joining Oxford University in 2009. There he developed screening assays for clinically relevant mutations, including KRAS, BRAF and JAK2, across a range of haematological malignancies. As part of his PhD from Oxford Brookes University in 2016, Adam developed targeted and whole genome sequencing approaches to help diagnose haematological malignancies. This work was subsequently adopted for routine diagnostic use in the Oxford University Hospitals NHS Foundation Trust and also informed the Genomics England 100,000 Genomes Project. Adam’s current research is centred on using nanopore sequencing, and other patient-near technologies, as an accurate, low-cost, easy-to-use screening platform to detect clinically relevant genetic changes in haematological malignancies for use in resource-poor regions of the world.
Burns, A. et al. Whole-genome sequencing of chronic lymphocytic leukaemia reveals distinct differences in the mutational landscape between IgHVmut and IgHVunmut subgroups. Leukemia 32, 332–342 (2018)
Stamatopoulos B, et al. Targeted deep sequencing reveals clinically relevant subclonal IgHV rearrangements in chronic lymphocytic leukemia. Leukemia 31, 837–845 (2017)
Pellagatti, A. et al. Targeted resequencing analysis of 31 genes commonly mutated in myeloid disorders in serial samples from myelodysplastic syndrome patients showing disease progression. Leukemia 30, 247–250 (2016)
Chronic Lymphocytic Leukaemia (CLL) is the most common form of leukaemia in the Western world, and is characterised by both clinical and biological heterogeneity. The majority of CLL patients display few symptoms at diagnosis, after which the disease can progress into either an aggressive, chemo-resistant form with poor prognosis, or a relatively indolent form with a life expectancy similar to that seen in the normal population. The path taken by any particular CLL case is influenced by the presence or absence of a number of specific molecular alterations, including copy number changes such as trisomy 12, del(11q), del(13q) and del(17p), the mutational status of the immunoglobulin heavy chain (IgHV), and the presence of somatic mutations within TP53. As such, identification of these changes is an important part of the treatment decision process. Here I will highlight our work using a combination of targeted and ultra-low coverage whole genome sequencing on the MinION platform, to simplify the detection of these clinically important molecular alterations in CLL.