Nature Genetics
14, 33 - 41 (1996)
doi:10.1038/ng0996-33
The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB−binding proteinJulian Borrow1, Vincent P. Stanton Jr1, J. Michael Andresen1, Reinhard Becher2, Frederick G. Behm3, Raju S. K. Chaganti4, Curt I. Civin5, Christine Disteche6, Ian Dubé7, Anna Marie Frischauf8, Doug Horsman9, Felix Mitelman10, Stefano Volinia11, Ann E. Watmore12
& David E. Housman1
1Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
2West German Cancer Center, Hufelandstr55, 45122 Essen 1, Germany
3St.Jude Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee 38101, USA
4Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA
5The John Hopkins Oncology Center, 600 N.Wolfe Street, Baltimore, Maryland 21287, USA
6University of Washington Medical Center, Seattle, Washington 98195, USA
7Sunnybrook Health Science Centre, University of Toronto, 2075 Bayview Avenue, Toronto, M4N 3M5, Canada
8Imperial Cancer Research Fund, PO Box 123, Lincoln's Inn Fields, London, WC2 A3PX, UK
9British Columbia Cancer Agency, 600 West 1 Oth Avenue, Vancouver, British Columbia, V5Z 4E6, Canada
10Department of Clinical Genetics, University Hospital, S-22185 Lund, Sweden
11Universita'delgi Studi, Via Borsari 46, 44100 Ferrara, Italy
12Centre for Human Genetics, 117 Manchester Road, Sheffield, S10 5DN, UK The recurrent translocation t(8;16)(p11 ;p13) is a cytogenetic hallmark for the M4/M5 subtype of acute myeloid leukaemia. Here we identify the breakpoint-associated genes. Positional cloning on chromosome 16 implicates the CREB-binding protein (CBP), a transcriptional adaptor/coactivator protein. At the chromosome 8 breakpoint we identify a novel gene, MOZ, which encodes a 2,004-amino-acid protein characterized by two C4HC3 zinc fingers and a single C2HC zinc finger in conjunction with a putative acetyltransferase signature. In-frame MOZ−CBP fusion transcripts combine the MOZ finger motifs and putative acetyltransferase domain with a largely intact CBP. We suggest that MOZ may represent a chromatin-associated acetyltransferase, and raise the possibility that a dominant MOZ−CBP fusion protein could mediate leukaemogenesis via aberrant chromatin acetylation.
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