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dc.contributor.authorPanagopoulos, Ioannis
dc.contributor.authorBrunetti, Marta
dc.contributor.authorStoltenberg, Margrethe
dc.contributor.authorStrandabø, Rønnaug
dc.contributor.authorStaurseth, Julie
dc.contributor.authorAndersen, Kristin
dc.contributor.authorKostolomov, Ilya
dc.contributor.authorHveem, Tarjei Sveinsgjerd
dc.contributor.authorLorenz, Susanne
dc.contributor.authorNystad, Tove Anita
dc.contributor.authorFlægstad, Trond
dc.contributor.authorMicci, Francesca
dc.contributor.authorHeim, Sverre
dc.date.accessioned2019-09-27T11:43:25Z
dc.date.available2019-09-27T11:43:25Z
dc.date.issued2019-05-29
dc.description.abstract<i>Background</i> - Many cases of acute lymphoblastic leukemia (ALL) carry visible acquired chromosomal changes of pathogenetic, diagnostic, and prognostic importance. Nevertheless, from one-fourth to half of newly diagnosed ALL patients have no visible chromosomal changes detectable by G-banding analysis at diagnosis. The introduction of powerful molecular methodologies has shown that many karyotypically normal ALLs carry clinically important submicroscopic aberrations.<p> <p><i>Case presentation</i> - We used fluorescence in situ hybridization (FISH), array comparative genomic hybridization (aCGH), RNA sequencing, reverse transcription (RT) and genomic polymerase chain reaction (PCR), as well as Sanger sequencing to investigate a case of pediatric ALL with a normal karyotype. FISH with a commercial <i>PDGFRB</i> breakapart probe showed loss of the distal part of the probe suggesting a breakpoint within the <i>PDGFRB</i> locus. aCGH revealed submicroscopic deletions in chromosome bands 5q32q35.3 (about 30 Mb long, starting within <i>PDGFRB</i> and finishing in the <i>CANX</i> locus), 7q34 (within <i>TCRB</i>), 9p13 (<i>PAX5</i>), 10q26.13 (<i>DMBT1</i>), 14q11.2 (<i>TRAC</i>), and 14q32.33 (within the <i>IGH</i> locus). RNA sequencing detected an in-frame <i>GTF2I–PDGFRB</i> and an out-of-frame <i>IKZF1–TYW1</i> fusion transcript. Both fusion transcripts were verified by RT-PCR together with Sanger sequencing and interphase FISH. The <i>GTF2I–PDGFRB</i> fusion was also verified by genomic PCR and FISH. The corresponding <i>GTF2I–PDGFRB</i> fusion protein would consist of almost the entire GTF2I and that part of PDGFRB which harbors the catalytic domain of the tyrosine kinase. It would therefore seem to lead to abnormal tyrosine kinase activity in a manner similar to what has been seen for other PDGFRB fusion proteins.<p> <p><i>Conclusions</i> - The examined pediatric leukemia is a Ph-like ALL which carries novel <i>GTF2I–PDGFRB</i> and <i>IKZF1–TYW1</i> fusion genes together with additional submicroscopic deletions. Because hematologic neoplasms with <i>PDGFRB</i>-fusion genes can be treated with tyrosine kinase inhibitors, the detection of such novel fusions may be clinically important. Since the <i>GTF2I–PDGFRB</i> could be detected only after molecular studies of the leukemic cells, further investigations of ALL-cases, perhaps especially but not exclusively with a normal karyotype, are needed in order to determine the frequency of <i>GTF2I–PDGFRB</i> in leukemia, and also to find out which clinical impact the fusion may have.en_US
dc.description.sponsorshipRadiumhospitalets Legateren_US
dc.descriptionSource at <a href=https://doi.org/10.1186/s40164-019-0136-y>https://doi.org/10.1186/s40164-019-0136-y. </a> © The Author(s) 2019en_US
dc.identifier.citationPanagopoulos, I., Brunetti, M., Stoltenberg, M., Strandabø, R.A.U., Staurseth, J., Andersen, K. ... Heim, S. (2019). Novel <i>GTF2I-PDGFRB</i> and <i>IKZF1-TYW1</i> fusions in pediatric leukemia with normal karyotype. <i>Experimental hematology and oncology, 8</i>:12. https://doi.org/10.1186/s40164-019-0136-yen_US
dc.identifier.cristinIDFRIDAID 1711647
dc.identifier.doi10.1186/s40164-019-0136-y
dc.identifier.issn2162-3619
dc.identifier.urihttps://hdl.handle.net/10037/16286
dc.language.isoengen_US
dc.publisherBMCen_US
dc.relation.journalExperimental hematology and oncology
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710en_US
dc.subjectPediatric acute lymphoblastic leukemiaen_US
dc.subjectNormal karyotypeen_US
dc.subjectSubmicroscopic deletionsen_US
dc.subjectFusion genesen_US
dc.subjectGTF2I–PDGFRBen_US
dc.subjectFluorescence in situ hybridizationen_US
dc.subjectArray comparative genomic hybridizationen_US
dc.subjectRNA sequencingen_US
dc.subjectGTF2I–PDGFRBen_US
dc.subjectIKZF1–TYW1en_US
dc.titleNovel GTF2I-PDGFRB and IKZF1-TYW1 fusions in pediatric leukemia with normal karyotypeen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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