Professor Bryan Young

Professor Bryan Young's main research themes are in: Bioinformatics, Cancer Genetics, Cancer Genomics, Haematological Malignancies and Microarray Technology

I established the cancer genomics group supported by Cancer Research UK at St Bartholomews Hospital. The work of our group has focused on haematological malignancy and led to several key observations.

A hallmark of most human cancers is the acquisition of chromosomal abnormalities. Many examples of chromosomal translocations have first been described in acute leukaemias and been shown to result in gene fusions. Increasingly such events are also being described in solid tumours. The prognostic importance of the karyotype is particularly well established for acute myeloid leukaemias (AML) which can be placed into good, intermediate or poor subgroups. Gene expression arrays have been used to demonstrate that each aberrant gene fusion event in AML is associated with a distinctive signature of up and down regulated genes.  Other genetic events that contribute to leukaemogenesis include recurrent point mutations and deletions.

The introduction of array and high throughput sequence (HTS) based technologies is uncovering previously unsuspected abnormalities that play a role in leukaemia etiology and progression. The presence of recurrent focal microdeletions in acute lymphoid leukaemia (ALLs) in adults has been described. Thus, 70% of the cases displayed deletion of one or more of the CDKN2A, PAX5, IKZF1, ETV6, RB1, and EBF1 genes.

Another form of unsuspected abnormality is the occurrence of partial uniparental disomy (UPD) acquired as a consequence of somatic recombination. We have shown that this abnormality occurs in 17% of AMLs and renders cells homozygous for particular mutations (eg FLT3). Furthermore we have demonstrated that UPD appears to be associated with relapse in AML and thus is one mechanism of disease progression. Significant disturbances in microRNA expression and DNA methylation in AML are also now being identified by HTS approaches. Establishing the complete genomic landscape in leukaemia is leading to novel therapeutic approaches.