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Genomic disruption ...
Genomic disruption of the histone methyltransferase SETD2 in chronic lymphocytic leukaemia
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- Parker, H. (author)
- Univ Southampton, Fac Med, Canc Res UK Ctr, Acad Unit Canc Sci, Southampton, Hants, England.;Univ Southampton, Expt Canc Med Ctr, Southampton, Hants, England.
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- Rose-Zerilli, M. J. J. (author)
- Univ Southampton, Fac Med, Canc Res UK Ctr, Acad Unit Canc Sci, Southampton, Hants, England.;Univ Southampton, Expt Canc Med Ctr, Southampton, Hants, England.
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- Larrayoz, M. (author)
- Univ Southampton, Fac Med, Canc Res UK Ctr, Acad Unit Canc Sci, Southampton, Hants, England.;Univ Southampton, Expt Canc Med Ctr, Southampton, Hants, England.
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- Clifford, R. (author)
- Univ Oxford, Mol Diagnost Ctr, Biomed Res Ctr, Oxford Natl Inst Hlth Res, Oxford, England.
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- Edelmann, J. (author)
- Univ Ulm, Dept Internal Med 3, Ulm, Germany.
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- Blakemore, S. (author)
- Univ Southampton, Fac Med, Canc Res UK Ctr, Acad Unit Canc Sci, Southampton, Hants, England.;Univ Southampton, Expt Canc Med Ctr, Southampton, Hants, England.
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- Gibson, J. (author)
- Univ Southampton, Fac Nat & Environm Sci, Ctr Biol Sci, Southampton, Hants, England.
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- Wang, J. (author)
- Queen Marys Univ London, Barts Canc Inst, Ctr Mol Oncol, London, England.
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- Ljungström, Viktor (author)
- Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab
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- Wojdacz, T. K. (author)
- Univ Southampton, Fac Med, Canc Res UK Ctr, Acad Unit Canc Sci, Southampton, Hants, England.;Univ Southampton, Expt Canc Med Ctr, Southampton, Hants, England.
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- Chaplin, T. (author)
- Queen Marys Univ London, Barts Canc Inst, Ctr Mol Oncol, London, England.
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- Roghanian, A. (author)
- Univ Southampton, Fac Med, Canc Res UK Ctr, Acad Unit Canc Sci, Southampton, Hants, England.;Univ Southampton, Expt Canc Med Ctr, Southampton, Hants, England.
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- Davis, Z. (author)
- Royal Bournemouth Hosp, Dept Mol Pathol, Bournemouth, Dorset, England.
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- Parker, A. (author)
- Royal Bournemouth Hosp, Dept Mol Pathol, Bournemouth, Dorset, England.
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- Tausch, E. (author)
- Univ Ulm, Dept Internal Med 3, Ulm, Germany.
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- Ntoufa, S. (author)
- Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
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- Ramos, S. (author)
- Univ Oxford, Mol Diagnost Ctr, Biomed Res Ctr, Oxford Natl Inst Hlth Res, Oxford, England.
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- Robbe, P. (author)
- Univ Oxford, Mol Diagnost Ctr, Biomed Res Ctr, Oxford Natl Inst Hlth Res, Oxford, England.
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- Alsolami, R. (author)
- Univ Oxford, Mol Diagnost Ctr, Biomed Res Ctr, Oxford Natl Inst Hlth Res, Oxford, England.
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- Steele, A. J. (author)
- Univ Southampton, Fac Med, Canc Res UK Ctr, Acad Unit Canc Sci, Southampton, Hants, England.;Univ Southampton, Expt Canc Med Ctr, Southampton, Hants, England.
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- Packham, G. (author)
- Univ Southampton, Fac Med, Canc Res UK Ctr, Acad Unit Canc Sci, Southampton, Hants, England.;Univ Southampton, Expt Canc Med Ctr, Southampton, Hants, England.
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- Rodriguez-Vicente, A. E. (author)
- Univ Salamanca, Univ Hosp Salamanca, CSIC,Dept Haematol, Comprehens Canc Ctr Res,IBMCC,Biomed Res Inst Sal, Salamanca, Spain.
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- Brown, L. (author)
- Univ Southampton, Fac Med, Canc Res UK Ctr, Acad Unit Canc Sci, Southampton, Hants, England.;Univ Southampton, Expt Canc Med Ctr, Southampton, Hants, England.
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- McNicholl, F. (author)
- Altnagelvin Hosp, Western Hlth & Social Care Trust, Derry, Londonderry, North Ireland.
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- Forconi, F. (author)
- Univ Southampton, Fac Med, Canc Res UK Ctr, Acad Unit Canc Sci, Southampton, Hants, England.;Univ Southampton, Expt Canc Med Ctr, Southampton, Hants, England.
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- Pettitt, A. (author)
- Royal Liverpool & Broadgreen Univ Hosp NHS Trust, Dept Mol & Clin Canc Med, Liverpool, Merseyside, England.
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- Hillmen, P. (author)
- St James Univ Hosp, Dept Haematol, Leeds, W Yorkshire, England.
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- Dyer, M. (author)
- Univ Leicester, Coll Med Biol Sci & Psychol, Leicester, Leics, England.
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- Cragg, M. S. (author)
- Univ Southampton, Fac Med, Canc Res UK Ctr, Acad Unit Canc Sci, Southampton, Hants, England.;Univ Southampton, Expt Canc Med Ctr, Southampton, Hants, England.
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Chelala, C. (author)
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- Oakes, C. C. (author)
- Ohio State Univ, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA.
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- Rosenquist, Richard (author)
- Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab
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- Stamatopoulos, K. (author)
- Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
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- Stilgenbauer, S. (author)
- Univ Ulm, Dept Internal Med 3, Ulm, Germany.
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- Knight, S. (author)
- Univ Oxford, Mol Diagnost Ctr, Biomed Res Ctr, Oxford Natl Inst Hlth Res, Oxford, England.
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Schuh, A. (author)
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- Oscier, D. G. (author)
- Univ Southampton, Fac Med, Canc Res UK Ctr, Acad Unit Canc Sci, Southampton, Hants, England.;Univ Southampton, Expt Canc Med Ctr, Southampton, Hants, England.;Royal Bournemouth Hosp, Dept Mol Pathol, Bournemouth, Dorset, England.
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- Strefford, J. C. (author)
- Univ Southampton, Fac Med, Canc Res UK Ctr, Acad Unit Canc Sci, Southampton, Hants, England.;Univ Southampton, Expt Canc Med Ctr, Southampton, Hants, England.
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Univ Southampton, Fac Med, Canc Res UK Ctr, Acad Unit Canc Sci, Southampton, Hants, England;Univ Southampton, Expt Canc Med Ctr, Southampton, Hants, England. Univ Oxford, Mol Diagnost Ctr, Biomed Res Ctr, Oxford Natl Inst Hlth Res, Oxford, England. (creator_code:org_t)
- 2016-05-20
- 2016
- English.
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In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 30:11, s. 2179-2186
- Related links:
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https://uu.diva-port... (primary) (Raw object)
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
Close
- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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Leukemia
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To the university's database
- By the author/editor
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Parker, H.
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Rose-Zerilli, M. ...
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Larrayoz, M.
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Clifford, R.
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Edelmann, J.
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Blakemore, S.
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show more...
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Gibson, J.
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Wang, J.
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Ljungström, Vikt ...
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Wojdacz, T. K.
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Chaplin, T.
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Roghanian, A.
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Davis, Z.
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Parker, A.
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Tausch, E.
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Ntoufa, S.
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Ramos, S.
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Robbe, P.
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Alsolami, R.
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Steele, A. J.
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Packham, G.
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Rodriguez-Vicent ...
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Brown, L.
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McNicholl, F.
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Forconi, F.
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Pettitt, A.
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Hillmen, P.
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Dyer, M.
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Cragg, M. S.
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Chelala, C.
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Oakes, C. C.
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Rosenquist, Rich ...
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Stamatopoulos, K ...
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Stilgenbauer, S.
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Knight, S.
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Schuh, A.
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Oscier, D. G.
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Strefford, J. C.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Leukemia
- By the university
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Uppsala University