Please use this identifier to cite or link to this item:
|Title:||Genomic disruption of the histone methyltransferase SETD2 in chronic lymphocytic leukaemia|
Rose-Zerilli, M. J. J.
Wojdacz, T. K.
Steele, A. J.
Rodríguez-Vicente, A. E.
Dyer, Martin J. S.
Cragg, M. S.
Oakes, C. C.
Oscier, D. G.
Strefford, J. C.
|Publisher:||Nature Publishing Group|
|Citation:||Leukemia, 2016, 30 (11), pp. 2179-2186|
|Abstract:||Histone methyltransferases (HMTs) are important epigenetic regulators of gene transcription and are disrupted at the genomic level in a spectrum of human tumours including haematological malignancies. Using high-resolution single nucleotide polymorphism (SNP) arrays, we identified recurrent deletions of the SETD2 locus in 3% (8/261) of chronic lymphocytic leukaemia (CLL) patients. Further validation in two independent cohorts showed that SETD2 deletions were associated with loss of TP53, genomic complexity and chromothripsis. With next-generation sequencing we detected mutations of SETD2 in an additional 3.8% of patients (23/602). In most cases, SETD2 deletions or mutations were often observed as a clonal event and always as a mono-allelic lesion, leading to reduced mRNA expression in SETD2-disrupted cases. Patients with SETD2 abnormalities and wild-type TP53 and ATM from five clinical trials employing chemotherapy or chemo-immunotherapy had reduced progression-free and overall survival compared with cases wild type for all three genes. Consistent with its postulated role as a tumour suppressor, our data highlight SETD2 aberration as a recurrent, early loss-of-function event in CLL pathobiology linked to aggressive disease.|
|Rights:||Copyright © the authors, 2016. This is an open-access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
|Appears in Collections:||Published Articles, College of Medicine, Biological Sciences and Psychology|
Files in This Item:
|Genomic disruption of the histone methyltransferase SETD2 in chronic lymphocytic leukaemia.pdf||Published (publisher PDF)||1.06 MB||Adobe PDF||View/Open|
Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.