NUP98 rearrangements in hematopoietic malignancies: a study of the Groupe Francophone de Cytogénétique Hématologique.
The NUP98 gene is fused with 19 different partner genes in various human hematopoietic malignancies. In order to gain additional clinico-hematological data and to identify new partners of NUP98, the Groupe Francophone de Cytogénétique Hématologique (GFCH) collected cases of hematological malignancies where a 11p15 rearrangement was detected. Fluorescence in situ hybridization (FISH) analysis showed that 35% of these patients (23/66) carried a rearrangement of the NUP98 locus. Genes of the HOXA cluster and the nuclear-receptor set domain (NSD) genes were frequently fused to NUP98, mainly in de novo myeloid malignancies whereas the DDX10 and TOP1 genes were equally rearranged in de novo and in therapy-related myeloid proliferations. Involvement of ADD3 and C6ORF80 genes were detected, respectively, in myeloid disorders and in T-cell acute lymphoblastic leukemia (T-ALL), whereas the RAP1GDS1 gene was fused to NUP98 in T-ALL. Three new chromosomal breakpoints: 3q22.1, 7p15 (in a localization distinct from the HOXA locus) and Xq28 were detected in rearrangements with the NUP98 gene locus. The present study as well as a review of the 73 cases previously reported in the literature allowed us to delineate some chromosomal, clinical and molecular features of patients carrying a NUP98 gene rearrangements.
Service de cytogénétique, Centre Hospitalier Universitaire (CHU) Necker-Enfants Malades, Paris, France. serge.romana@nck.ap-hop-paris.fr
S P
SP
Romana
I
I
Radford-Weiss
R
R
Ben Abdelali
C
C
Schluth
A
A
Petit
N
N
Dastugue
P
P
Talmant
C
C
Bilhou-Nabera
F
F
Mugneret
M
M
Lafage-Pochitaloff
M-J
MJ
Mozziconacci
J
J
Andrieu
J-L
JL
Lai
C
C
Terre
K
K
Rack
P
P
Cornillet-Lefebvre
I
I
Luquet
N
N
Nadal
F
F
Nguyen-Khac
C
C
Perot
J
J
Van den Akker
S
S
Fert-Ferrer
C
C
Cabrol
C
C
Charrin
I
I
Tigaud
H
H
Poirel
M
M
Vekemans
O A
OA
Bernard
R
R
Berger
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D020732:Cytogenetic Analysis; D005260:Female; D005602:France; D019337:Hematologic Neoplasms / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D008875:Middle Aged; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D012955:Societies, Medical; D014178:Translocation, Genetic / Q000235:genetics*
D018398:Homeodomain Proteins; D028861:Nuclear Pore Complex Proteins; C465451:Nup98 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; C088144:HoxA protein