title: Cryptic insertion producing two NUP98/NSD1 chimeric transcripts in adult refractory anemia with an excess of blasts.
abstract: We performed cytogenetic and molecular studies on an adult patient with refractory anemia with an excess of blasts with an add(11)(p15). Multicolor fluorescence in situ hybridization (FISH) identified the extra material on 11p as belonging to chromosome 15. Metaphase FISH with probes for chromosomes 5, 11, and 15 revealed a complex four-break rearrangement. Clone RP5-1173K1, containing exons 10-20 of the NUP98 gene, gave three fluorescence signals on the normal 11, the der(5), and the der(15). 3'-RACE-PCR identified an in-frame fusion between NUP98 and NSD1, which was confirmed by RT-PCR. Two different spliced forms, that is, NUP98 exon 11/NSD1 exon 6 and NUP98 exon 12/NSD1 exon 6, were detected. The reciprocal NSD1/NUP98 was not found. A dual-color experiment with RP5-1173K1 and CTC-549A4, spanning the entire NSD1 gene, indicated an insertion of NUP98 into the NSD1 locus. This is the first report of an adult with myelodysplastic syndrome (MDS) harboring an NUP98/NSD1 fusion resulting from insertion of 5'-NUP98 into the NSD1/5q35 locus.
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, University of Perugia, 06123 Perugia, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: La Starza
authors.forename: Paolo
authors.initials: P
authors.lastname: Gorello
authors.forename: Roberto
authors.initials: R
authors.lastname: Rosati
authors.forename: Antonio
authors.initials: A
authors.lastname: Riezzo
authors.forename: Angelo
authors.initials: A
authors.lastname: Veronese
authors.forename: Eros
authors.initials: E
authors.lastname: Ferrazzi
authors.forename: Massimo F
authors.initials: MF
authors.lastname: Martelli
authors.forename: Massimo
authors.initials: M
authors.lastname: Negrini
authors.forename: Cristina
authors.initials: C
authors.lastname: Mecucci
mesh_terms: D000595:Amino Acid Sequence; D000753:Anemia, Refractory / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D019457:Chromosome Breakage; D002880:Chromosomes, Human, Pair 11; D002884:Chromosomes, Human, Pair 15; D002895:Chromosomes, Human, Pair 5; D005091:Exons; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; C093350:nuclear pore complex protein 98; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C113272:NSD1 protein, human