Using a well-known field of mathematics – information theory – researchers have uncovered possible genes involved in the development of a common childhood leukaemia.
Acute lymphoblastic leukaemia
Acute lymphoblastic leukaemia (ALL) is the most common form of cancer in children. It affects an estimated 3,000 children every year in the US alone. Emerging evidence has highlighted a critical role of epigenetic dysregulation in both the aetiology and progression of ALL.
However, current studies that aim to define epigenetic drivers have been limited by several factors. These include an emphasis on array-based techniques assessing only a few target regions, the scarcity of whole-genome bisulphite sequencing data and the statistical limitations of methylation inferences.
Information theory
In this study, published in Nature Biomedical Engineering, researchers conducted a comprehensive analysis, based on information theory, of the differences in methylation patterns in samples from patients with paediatric ALL. Information theory is a field of mathematics, represented by a string of zeros and ones, designed to study how digital and other forms of information are measured, stored and shared. The researchers specifically applied information theory to analyse the DNA methylation code – with a string of zeros and ones representing methylation or no methylation.
The team found regions of the genome that were consistently methylated across patients with leukaemia. They also found that epigenetic changes in ALL converged on a shared set of genes that overlapped with genetic drivers involved in chromosomal translocations. One gene in particular, the UHRF1 gene, had differences in DNA methylation compared with the normal genome. Experiments in the laboratory showed that leukaemia cells lacking this gene could not self-renew and propagate additional leukaemia cells.
The team plan to use information theory to analyse methylation patterns across other cancers. They also plan to further explore whether epigenetic alterations in URFH1 are linked to treatment resistance and disease progression in childhood leukaemia.
Image credit: By starline – freepik
