Professor Bryan Young
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.
1967-1971 PhD Faculty of Medicine, Glasgow University
1972-1984 Research Fellow, Beatson Institute, Glasgow
1985-1992 Senior lecturer and Group Leader
1993-present Professor of Cancer Genomics, Queen Mary University
2000-present Professor, Deputy Director of Medical Oncology Unit.
Honours and Awards
2011 Fellow of Academy of Medical Sciences
Cancer Research UK Program Grant
Dunne, J., D.M. Gascoyne, T.A. Lister, H.J. Brady, O. Heidenreich, and B.D. Young, AML1/ETO proteins control POU4F1/BRN3A expression and function in t(8;21) acute myeloid leukemia. Cancer Res, 2010. 70(10): p. 3985-95. PMID: 20460523
Raghavan, M., L.L. Smith, D.M. Lillington, T. Chaplin, I. Kakkas, G. Molloy, C. Chelala, J.B. Cazier, J.D. Cavenagh, J. Fitzgibbon, T.A. Lister, and B.D. Young, Segmental uniparental disomy is a commonly acquired genetic event in relapsed acute myeloid leukemia. Blood, 2008. 112(3): p. 814-21. PMID: 18490517
Paulsson, K., J.B. Cazier, F. Macdougall, J. Stevens, I. Stasevich, N. Vrcelj, T. Chaplin, D.M. Lillington, T.A. Lister, and B.D. Young, Microdeletions are a general feature of adult and adolescent acute lymphoblastic leukemia: Unexpected similarities with pediatric disease. Proc Natl Acad Sci U S A, 2008. 105(18): p. 6708-13. PMID: 18458336
Dixon-McIver, A., P. East, C.A. Mein, J.B. Cazier, G. Molloy, T. Chaplin, T. Andrew Lister, B.D. Young, and S. Debernardi, Distinctive patterns of microRNA expression associated with karyotype in acute myeloid leukaemia. PLoS One, 2008. 3(5): p. e2141. PMID: 18478077
For additional publications, please click here.
Cancer Genomics Group:
Jun Wang (Alec)
Editor of Genes Chromosome and Cancer