Chromosome 20 deletions in myeloid malignancies: reduction of the common deleted region, generation of a PAC/BAC contig and identification of candidate genes. UK Cancer Cytogenetics Group (UKCCG).
Anthony J. Bench,Elisabeth P. Nacheva,Tracey L. Hood,Jane L. Holden,Lisa French,Soheila Swanton,Kim Champion,Juan Li,Pamela Whittaker,George Stavrides,Adrienne Hunt,Brian Jp Huntly,Lynda J. Campbell,David R. Bentley,Panos Deloukas,Anthony R. Green +15 more
TLDR
Analysis of patients with a 20q deletion associated with a myeloid malignancy identifies a set of genes which are both positional and expression candidates for the target gene(s) on 20q, which is the most detailed physical map of this region to date.Abstract:
Deletion of the long arm of chromosome 20 represents the most common chromosomal abnormality associated with the myeloproliferative disorders (MPDs) and is also found in other myeloid malignancies including myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). Previous studies have identified a common deleted region (CDR) spanning approximately 8 Mb. We have now used G-banding, FISH or microsatellite PCR to analyse 113 patients with a 20q deletion associated with a myeloid malignancy. Our results define a new MPD CDR of 2.7 Mb, an MDS/AML CDR of 2.6 Mb and a combined 'myeloid' CDR of 1.7 Mb. We have also constructed the most detailed physical map of this region to date--a bacterial clone map spanning 5 Mb of the chromosome which contains 456 bacterial clones and 202 DNA markers. Fifty-one expressed sequences were localized within this contig of which 37 lie within the MPD CDR and 20 within the MDS/AML CDR. Of the 16 expressed sequences (six genes and 10 unique ESTs) within the 'myeloid' CDR, five were expressed in both normal bone marrow and purified CD34 positive cells. These data identify a set of genes which are both positional and expression candidates for the target gene(s) on 20q.read more
Citations
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A Gain-of-Function Mutation of JAK2 in Myeloproliferative Disorders
Robert Kralovics,Francesco Passamonti,Andreas Buser,Soon Siong Teo,Ralph Tiedt,Jakob Passweg,André Tichelli,Mario Cazzola,Radek C. Skoda +8 more
TL;DR: Genetic evidence and in vitro functional studies indicate that V617F gives hematopoietic precursors proliferative and survival advantages and a high proportion of patients with myeloproliferative disorders carry a dominant gain-of-function mutation of JAK2.
Journal ArticleDOI
Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders.
E. Joanna Baxter,Linda M. Scott,Peter J. Campbell,Clare L. East,Nasios Fourouclas,Soheila Swanton,George S. Vassiliou,Anthony J. Bench,Elaine M. Boyd,Natasha Curtin,Michael A. Scott,Wendy N. Erber,Anthony R. Green,Anthony R. Green +13 more
TL;DR: A single acquired mutation of JAK2 was noted in more than half of patients with a myeloproliferative disorder and its presence in all erythropoietin-independent erythroid colonies demonstrates a link with growth factor hypersensitivity, a key biological feature of these disorders.
Journal ArticleDOI
The myeloproliferative disorders.
TL;DR: The legacy of this discovery of an identical mutation of the JAK2 gene in patients with polycythemia vera, essential thrombocythemia, and myelofibrosis is reviewed.
Journal ArticleDOI
The DNA sequence and comparative analysis of human chromosome 20.
Panos Deloukas,M Earthrowl,Darren Grafham,Marc Rubenfield,Lisa French,Charles A. Steward,Sarah Sims,Matthew Jones,S. Searle,Carol Scott,Kerstin Howe,Sarah E. Hunt,T D Andrews,James G. R. Gilbert,David Swarbreck,Jennifer L. Ashurst,A Taylor,J Battles,Christine P. Bird,R Ainscough,J P Almeida,R I S Ashwell,K D Ambrose,A K Babbage,C L Bagguley,J Bailey,Ruby Banerjee,K Bates,Helen Beasley,S Bray-Allen,A J Brown,J Y Brown,D C Burford,W Burrill,John Burton,Patrick Cahill,D Camire,Nigel P. Carter,J C Chapman,S Y Clark,G Clarke,C M Clee,S. M. Clegg,N Corby,Alan Coulson,Pawandeep Dhami,I Dutta,Matthew Dunn,L M Faulkner,Adam Frankish,J Frankland,P Garner,J Garnett,Susan M. Gribble,C Griffiths,Russell J. Grocock,Erik Gustafson,S Hammond,Joanna Harley,E. Hart,Paul Heath,T P Ho,B Hopkins,J Horne,Philip Howden,Elizabeth J. Huckle,C Hynds,Chris Johnson,David W. Johnson,A Kana,M. Kay,A M Kimberley,J K Kershaw,M Kokkinaki,Gavin K. Laird,S Lawlor,H M Lee,Daniel Leongamornlert,G Laird,Christine Lloyd,D. M. Lloyd,Jane E. Loveland,J Lovell,Stuart McLaren,Kirsten McLay,Amanda McMurray,M Mashreghi-Mohammadi,Lucy Matthews,Sarah Milne,T Nickerson,M Nguyen,E K Overton-Larty,Sophie Palmer,A. V. Pearce,A I Peck,Sarah Pelan,Benjamin Phillimore,K M Porter,Catherine M. Rice,A Rogosin,Mark T. Ross,Theologia Sarafidou,Harminder Sehra,Ratna Shownkeen,C. D. Skuce,Michelle Smith,L Standring,N Sycamore,J Tester,A Thorpe,W Torcasso,Alan Tracey,A Tromans,J Tsolas,Melanie M. Wall,J Walsh,H Wang,Keith Weinstock,Anthony P. West,David Willey,S. Whitehead,Laurens G. Wilming,Paul Wray,L Young,Yuan Chen,Ruth C. Lovering,Nicholas K. Moschonas,Reiner Siebert,Kim Fechtel,David Bentley,Richard Durbin,Tim Hubbard,Lynn Doucette-Stamm,Stephan Beck,Douglas Smith,Jane Rogers +135 more
TL;DR: Comparative analysis of the sequence of chromosome 20 to whole-genome shotgun-sequence data of two other vertebrates provides an independent measure of the efficiency of gene annotation, and indicates that this analysis may account for more than 95% of all coding exons and almost all genes.
Journal ArticleDOI
Unraveling the Molecular Pathophysiology of Myelodysplastic Syndromes
TL;DR: Elucidation of the full complement of genetic causes of MDS promises profound insight into the biology of the disease, improved classification and prognostic scoring schemes, and the potential for novel targeted therapies with molecular predictors of response.
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