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CBP truncating mutations in ovarian cancer
  1. R Ward1,
  2. M Johnson1,
  3. V Shridhar1,
  4. J van Deursen2,3,
  5. F J Couch1,3
  1. 1Departments of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, USA
  2. 2Departments of Pediatrics, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, USA
  3. 3Departments of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, USA
  1. Correspondence to:
 Dr F J Couch
 Mayo Clinic, Department of Laboratory Medicine and Pathology, 200 First Street SW, Rochester, MN 55905, USA;

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The CBP gene (OMIM #600140) encodes the 2441 amino acid cyclic AMP response element binding protein (CREB) binding protein (Mr 265 000) that functions as an essential co-activator for a number of transcription factors.1 In particular, CBP, like its homologue EP300, enhances gene transcription by linking sequence specific transcription factors to transcription factor IIB and the RNA polymerase II holoenzyme.2 CBP can also promote gene transcription by acetylation of histones through its histone acetyltransferase activity (HAT)3 and by acetylation of specific transcription factors such as p53.4–6 Several lines of evidence suggest the involvement of CBP in tumour formation. CBP interacts with the human T cell leukaemia virus (HTLV) Tax protein and v-myb to induce viral and cellular genes that promote cell transformation, while adenovirus E1A, simian virus SV40 Tag, and human papillomavirus (HPV) E6 bind to CBP and inhibit its co-activator function. CBP is also known to modulate the actions of the hMDM2 and AML1 cellular proto-oncogenes and the BRCA1 and p53 tumour suppressors.7 More direct evidence comes from genetic studies of translocation events involving CBP in leukaemia. In particular, the t(8;16)(p11;p13) translocation in AML involves a fusion of the CBP and MOZ genes,8 a novel t(10;16)(q22;p13) translocation in a childhood acute myelogenous leukaemia (AML-M5a) generates a MORF-CBP chimera,9 and the t(11;16)(q23;p13.3) translocation in topoisomerase II treated acute leukaemia or myelodysplasia results in a MLL-CBP fusion.10 In addition, haploinsufficiency of CBP in humans due to chromosomal rearrangements, microdeletions, and point mutations results in Rubenstein-Taybi Syndrome (RTS), and is associated with an increased risk for a variety of tumours.11

As a result of these observations, a number of studies have evaluated whether CBP is a direct mutational target in cancer and has tumour suppressor activity. One recent mutation screening study of …

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  • Competing interests: none declared