title: Characterization of 6q abnormalities in childhood acute myeloid leukemia and identification of a novel t(6;11)(q24.1;p15.5) resulting in a NUP98-C6orf80 fusion in a case of acute megakaryoblastic leukemia.
abstract: Chromosome abnormalities of 6q are not frequently observed in myeloid disorders. In this article, we report the incidence of these chromosome changes in childhood myeloid leukemia as 2%-4% based on the cytogenetic database of a single institution. We applied fluorescence in situ hybridization (FISH) to characterize precisely the types of 6q abnormalities in seven patients (six with acute myeloid leukemia and one with myelodysplastic syndrome). They carried various translocations involving different breakpoints in 6q, as confirmed by FISH using a whole-chromosome-6 paint. Four cases were reported as t(6;11), although the breakpoints varied. Among these, we identified a novel translocation, t(6;11)(q24.1;p15.5), in a patient with acute megakaryoblastic leukemia. Molecular cytogenetic studies using the PAC clone RP5-1173K1 localized the genomic breakpoint on chromosome 11 to within the NUP98 gene. The breakpoint on chromosome 6 was narrowed down to a 500-kb region between BAC clones RP11-721P14 and RP11-39H10. Reverse-transcription PCR was performed using a forward primer specific for NUP98 and a reverse primer for the candidate gene in the 500-kb interval in 6q. This experiment resulted in the identification of a new fusion between NUP98 and C6orf80. Further studies will aim to fully characterize C6orf80 and will elucidate the role of this new NUP98 fusion in myeloid leukemia.
authors: Leukaemia Research Fund Molecular Haematology Unit, Nuffield Department of Clinical Laboratory Science, John Radcliffe Hospital, Oxford, United Kingdom. sabrina.tosi@ndcls.ox.ac.uk
authors: Sabrina
authors: S
authors: Tosi
authors: Erica
authors: E
authors: Ballabio
authors: Andrea
authors: A
authors: Teigler-Schlegel
authors: Jackie
authors: J
authors: Boultwood
authors: Jochen
authors: J
authors: Bruch
authors: Jochen
authors: J
authors: Harbott
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D019457:Chromosome Breakage; D022202:Chromosomes, Artificial, Bacterial; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D020732:Cytogenetic Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007951:Leukemia, Myeloid / Q000235:genetics*; D008969:Molecular Sequence Data; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic
chemical_list: D004273:DNA, Neoplasm; D028861:Nuclear Pore Complex Proteins; D015514:Oncogene Proteins, Fusion; D012334:RNA, Neoplasm; C093350:nuclear pore complex protein 98