title: Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukaemia.
abstract: Expression of Hoxa7 and Hoxa9 is activated by proviral integration in BXH2 murine myeloid leukaemias. This result, combined with the mapping of the HOXA locus to human chromosome 7p15, suggested that one of the HOXA genes might be involved in the t(7;11)(p15;p15) translocation found in some human myeloid leukaemia patients. Here we show that in three patients with t(7;11), the chromosome rearrangement creates a genomic fusion between the HOXA9 gene and the nucleoporin gene NUP98 on chromosome 11p15. The translocation produces an invariant chimaeric NUP98/HOXA9 transcript containing the amino terminal half of NUP98 fused in frame to HOXA9. These studies identify HOXA9 as an important human myeloid leukaemia gene and suggest an important role for nucleoporins in human myeloid leukaemia given that a second nucleoporin, NUP214, has also been implicated in human myeloid leukaemia.
authors.affiliation: Mammalian Genetics Laboratory, NCI-Frederick Cancer Research and Development Center, Maryland 21702, USA.
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: D A
authors.initials: DA
authors.lastname: Largaespada
authors.forename: M P
authors.initials: MP
authors.lastname: Lee
authors.forename: L A
authors.initials: LA
authors.lastname: Johnson
authors.forename: K
authors.initials: K
authors.lastname: Ohyashiki
authors.forename: K
authors.initials: K
authors.lastname: Toyama
authors.forename: S J
authors.initials: SJ
authors.lastname: Chen
authors.forename: C L
authors.initials: CL
authors.lastname: Willman
authors.forename: I M
authors.initials: IM
authors.lastname: Chen
authors.forename: A P
authors.initials: AP
authors.lastname: Feinberg
authors.forename: N A
authors.initials: NA
authors.lastname: Jenkins
authors.forename: N G
authors.initials: NG
authors.lastname: Copeland
authors.forename: J D
authors.initials: JD
authors.lastname: Shaughnessy
mesh_terms: D000208:Acute Disease; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11; D002897:Chromosomes, Human, Pair 7; D003001:Cloning, Molecular; D005801:Genes, Homeobox / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D007951:Leukemia, Myeloid / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D015183:Restriction Mapping; D017422:Sequence Analysis, DNA; D014178:Translocation, Genetic
chemical_list: D018398:Homeodomain Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C097899:homeobox protein HOXA9; C093350:nuclear pore complex protein 98