Many BCR-ABL1 compound mutations reported in chronic myeloid leukemia patients may actually be artifacts due to PCR-mediated recombination

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dc.contributor.authorParker, W.
dc.contributor.authorPhillis, S.
dc.contributor.authorYeung, D.
dc.contributor.authorHughes, T.
dc.contributor.authorScott, H.
dc.contributor.authorBranford, S.
dc.date.issued2014
dc.descriptionLetter to the editor
dc.description.abstractBCR-ABL1 kinase domain (KD) mutations are the most common known cause of treatment failure in chronic myeloid leukemia (CML). Emerging evidence suggests that compound mutations (>1 KD mutation in the same molecule) confer resistance to ponatinib and combination therapy (GNF-5/nilotinib). Surprisingly, however, in most cases reported, the same mutations were found both as compound mutations and as individual mutations in the same patient, suggesting that the same nucleotide substitution occurred independently multiple times within an individual patient. Based on extensive evidence that PCR frequently mediates recombination between highly similar templates and generates chimeric amplicons containing sequence from >1 different alleles, we argue that the mutant complexity reported maybe inflated due to PCR artifacts.
dc.description.statementofresponsibilityWendy T. Parker, Stuart R. Phillis, David T. O. Yeung, Timothy P. Hughes, Hamish S. Scott, and Susan Branford
dc.identifier.citationBlood, 2014; 124(1):153-155
dc.identifier.doi10.1182/blood-2014-05-573485
dc.identifier.issn0006-4971
dc.identifier.issn1528-0020
dc.identifier.orcidYeung, D. [0000-0002-7558-9927]
dc.identifier.orcidHughes, T. [0000-0002-0910-3730] [0000-0002-7990-4509]
dc.identifier.orcidScott, H. [0000-0002-5813-631X]
dc.identifier.orcidBranford, S. [0000-0002-1964-3626] [0000-0002-5095-7981]
dc.identifier.urihttp://hdl.handle.net/2440/90033
dc.language.isoen
dc.publisherAmerican Society of Hematology
dc.rights© 2014 by The American Society of Hematology
dc.source.urihttps://doi.org/10.1182/blood-2014-05-573485
dc.subjectFusion Proteins, bcr-abl
dc.subjectPolymerase Chain Reaction
dc.subjectMutation
dc.subjectLeukemia, Myelogenous, Chronic, BCR-ABL Positive
dc.subjectArtifacts
dc.titleMany BCR-ABL1 compound mutations reported in chronic myeloid leukemia patients may actually be artifacts due to PCR-mediated recombination
dc.typeJournal article
pubs.publication-statusPublished

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