Journal article
Cooperativity of imprinted genes inactivated by acquired chromosome 20q deletions
A Aziz, EJ Baxter, C Edwards, CY Cheong, M Ito, A Bench, R Kelley, Y Silber, PA Beer, K Chng, MB Renfree, K McEwen, D Gray, J Nangalia, GJ Mufti, E Hellstrom-Lindberg, JJ Kiladjian, MF McMullin, PJ Campbell, AC Ferguson-Smith Show all
Journal of Clinical Investigation | Published : 2013
DOI: 10.1172/JCI66113
Abstract
Large regions of recurrent genomic loss are common in cancers; however, with a few well-characterized exceptions, how they contribute to tumor pathogenesis remains largely obscure. Here we identified primate-restricted imprinting of a gene cluster on chromosome 20 in the region commonly deleted in chronic myeloid malignancies. We showed that a single heterozygous 20q deletion consistently resulted in the complete loss of expression of the imprinted genes L3MBTL1 and SGK2, indicative of a pathogenetic role for loss of the active paternally inherited locus. Concomitant loss of both L3MBTL1 and SGK2 dysregulated erythropoiesis and megakaryopoiesis, 2 lineages commonly affected in chronic myeloi..
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Grants
Awarded by Medical Research Council
Funding Acknowledgements
We are grateful to the staff of Cambridge Blood and Stem Cell Bio-bank for provision of samples and to Anna Petrunkina for flow cytometry support. We are also indebted to Matthew Hardy, David Kent, Juan Li, Geoff Shaw, Andy Pask, Rita Ferreira, and Nasios Fourouclas for advice and/or technical assistance. The A.R. Green laboratory is supported by Leukemia and Lymphoma Research, the Cambridge NIHR Biomedical Research Centre, Cancer Research UK, the Leukemia and Lymphoma Society, and the Cambridge Experimental Cancer Medicine Centre. The A.C. Ferguson-Smith laboratory is supported by the MRC and Wellcome Trust and by A*STAR. P.J. Campbell is a Wellcome Trust senior clinical fellow.