Please use this identifier to cite or link to this item: https://doi.org/10.1038/leu.2017.75
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dc.titleAPOBEC signature mutation generates an oncogenic enhancer that drives LMO1 expression in T-ALL
dc.contributor.authorLi, Z
dc.contributor.authorAbraham, B.J
dc.contributor.authorBerezovskaya, A
dc.contributor.authorFarah, N
dc.contributor.authorLiu, Y
dc.contributor.authorLeon, T
dc.contributor.authorFielding, A
dc.contributor.authorTan, S.H
dc.contributor.authorSanda, T
dc.contributor.authorWeintraub, A.S
dc.contributor.authorLi, B
dc.contributor.authorShen, S
dc.contributor.authorZhang, J
dc.contributor.authorMansour, M.R
dc.contributor.authorYoung, R.A
dc.contributor.authorLook, A.T
dc.date.accessioned2020-10-22T07:37:04Z
dc.date.available2020-10-22T07:37:04Z
dc.date.issued2017
dc.identifier.citationLi, Z, Abraham, B.J, Berezovskaya, A, Farah, N, Liu, Y, Leon, T, Fielding, A, Tan, S.H, Sanda, T, Weintraub, A.S, Li, B, Shen, S, Zhang, J, Mansour, M.R, Young, R.A, Look, A.T (2017). APOBEC signature mutation generates an oncogenic enhancer that drives LMO1 expression in T-ALL. Leukemia 31 (10) : 2057-2064. ScholarBank@NUS Repository. https://doi.org/10.1038/leu.2017.75
dc.identifier.issn08876924
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/179091
dc.description.abstractOncogenic driver mutations are those that provide a proliferative or survival advantage to neoplastic cells, resulting in clonal selection. Although most cancer-causing mutations have been detected in the protein-coding regions of the cancer genome; driver mutations have recently also been discovered within noncoding genomic sequences. Thus, a current challenge is to gain precise understanding of how these unique genomic elements function in cancer pathogenesis, while clarifying mechanisms of gene regulation and identifying new targets for therapeutic intervention. Here we report a C-to-T single nucleotide transition that occurs as a somatic mutation in noncoding sequences 4 kb upstream of the transcriptional start site of the LMO1 oncogene in primary samples from patients with T-cell acute lymphoblastic leukaemia. This single nucleotide alteration conforms to an APOBEC-like cytidine deaminase mutational signature, and generates a new binding site for the MYB transcription factor, leading to the formation of an aberrant transcriptional enhancer complex that drives high levels of expression of the LMO1 oncogene. Since APOBEC-signature mutations are common in a broad spectrum of human cancers, we suggest that noncoding nucleotide transitions such as the one described here may activate potent oncogenic enhancers not only in T-lymphoid cells but in other cell lineages as well. © 2017 Macmillan Publishers Limited, part of Springer Nature.
dc.publisherNature Publishing Group
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20201031
dc.subjectapolipoprotein B mRNA editing enzyme catalytic polypeptide like
dc.subjectcytidine deaminase
dc.subject5' untranslated region
dc.subjectapolipoprotein B mRNA editing enzyme catalytic polypeptide like
dc.subjectDNA
dc.subjectDNA binding protein
dc.subjectLIM protein
dc.subjectLMO1 protein, human
dc.subjectprotein c Myb
dc.subjectsmall interfering RNA
dc.subjecttranscription factor
dc.subjecttranscriptome
dc.subjecttumor protein
dc.subjectacute lymphoblastic leukemia
dc.subjectArticle
dc.subjectbinding site
dc.subjectchromatin immunoprecipitation
dc.subjectcontrolled study
dc.subjectgene frequency
dc.subjectgene mutation
dc.subjectgene translocation
dc.subjecthuman
dc.subjecthuman cell
dc.subjecthuman tissue
dc.subjectLMO1 gene
dc.subjectluciferase assay
dc.subjectlymphoid cell
dc.subjectoncogene
dc.subjectpriority journal
dc.subjectprotein binding
dc.subjectprotein motif
dc.subjectquantitative analysis
dc.subjectreverse transcription polymerase chain reaction
dc.subjectsingle nucleotide polymorphism
dc.subjectsomatic mutation
dc.subjecttranscription initiation site
dc.subject5' untranslated region
dc.subjectacute lymphoblastic leukemia
dc.subjectantagonists and inhibitors
dc.subjectbiosynthesis
dc.subjectchild
dc.subjectenhancer region
dc.subjectgene expression regulation
dc.subjectgenetics
dc.subjectJurkat cell line
dc.subjectmetabolism
dc.subjectnucleotide sequence
dc.subjectoncogene myb
dc.subjectpoint mutation
dc.subjectRNA interference
dc.subjecttumor cell line
dc.subject5' Untranslated Regions
dc.subjectAPOBEC Deaminases
dc.subjectBase Sequence
dc.subjectBinding Sites
dc.subjectCell Line, Tumor
dc.subjectChild
dc.subjectChromatin Immunoprecipitation
dc.subjectDNA, Neoplasm
dc.subjectDNA-Binding Proteins
dc.subjectEnhancer Elements, Genetic
dc.subjectGene Expression Regulation, Leukemic
dc.subjectGenes, myb
dc.subjectHumans
dc.subjectJurkat Cells
dc.subjectLIM Domain Proteins
dc.subjectNeoplasm Proteins
dc.subjectPoint Mutation
dc.subjectPolymorphism, Single Nucleotide
dc.subjectPrecursor T-Cell Lymphoblastic Leukemia-Lymphoma
dc.subjectProto-Oncogene Proteins c-myb
dc.subjectRNA Interference
dc.subjectRNA, Small Interfering
dc.subjectTranscription Factors
dc.subjectTranscriptome
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentDEPT OF MEDICINE
dc.description.doi10.1038/leu.2017.75
dc.description.sourcetitleLeukemia
dc.description.volume31
dc.description.issue10
dc.description.page2057-2064
dc.published.statePublished
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