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t(5;11)(q35;p15.5) NUP98/NSD1

Written2002-03Lyndal Kearney
Leukaemia Research Fund Centre, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK

(Note : for Links provided by Atlas : click)


ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
Atlas_Id 1209

Clinics and Pathology

Disease de novo acute myeloid leukemia (AML)
Phenotype / cell stem origin No specific subtype. Only 5 cases reported to date (1 AML-M1, 2 AML-M2, 2 AML-M4)
Epidemiology all 5 reported cases were children or young adults (age range 3-18 years). Male: female ratio 1.5:1


Cytogenetics Morphological The t(5;11)(q35;p15.5) is not detectable by G-banding. Three cases were reported as cryptic t(5;11) associated with del(5q); a further two cases were identified in apparently normal karyotypes.
Cytogenetics Molecular In one FISH study using whole chromosome paints, three out of four cases of childhood AML with del(5q) as the sole cytogenetic abnormality were found to have a cryptic t(5;11). In a second study using chromosome-specific subtelomeric probes, two out of 31 children and young adults (19 years) with a normal G-banded karyotype were found to have a cryptic t(5;11).
Note: While the der(11) is detectable by single colour painting using chromosome 5 whole chromosome paint (WCP), the der(5) is not detectable using chromosome 11 WCP. Neither M-FISH or SKY can reliably detect the t(5;11).
  Fig 1. Identification of a cryptic t(5;11) using the M-TEL assay. Bone marrow metaphase from a normal karyotype AML child hybridized with the M-TEL1 probe set. Chromosomes 1, 3, 7, 9, 13, 15, 17, 19, 21 and X and Y probes were all correctly hybridized. However, one homologue of chromosome 5 has chromosome 11 material on the q arm (yellow), and the corresponding chromosome 11 homologue has chromosome 5 material on the p arm (green). This corresponds to a balanced translocation, t(5q;11p). The der(5) and der(11) are indicated by arrows.

Genes involved and Proteins

Gene NameNUP98 (nucleoporin 98 kDa)
Location 11p15.4
Note at least 8 different fusion partners for NUP98 in leukaemia
Dna / Rna Two major transcripts: 4.0 and 7.0 kb. The 4.0 kb transcript consists of 20 exons.
Protein 98 kD protein. Component of the nuclear pore complex, which regulates nucleocytoplasmic transport of protein and RNA. Contains multiple phenylalanine-glycine (FG) repeats which act as 'docking' sites for transport receptors.
Gene NameNSD1 (Nuclear receptor-binding, su (var), enhancer-of-zeste and trithorax domain-containing protein 1
Location 5q35.2
Dna / Rna at least 21 exons, cDNA is 8552 bp, open reading frame of 8088 bp
Protein predicted protein of 2696 amino acids. Contains at least 6 functional domains: su(var)3-9, enhancer-of-zeste, trithorax (SET), proline-tryptophan-tryptophan-proline (PWWP-I, PWWP-II), plant homeodomain protein­finger domains (PHD-I, PHD-II, PHD-III) and ten putative nuclear localization signals.

Result of the chromosomal anomaly

Hybrid gene
Note reciprocal NSD1-NUP98 fusion also present in all cases tested
Description The NUP98 and NSD1 mRNA are fused in-frame joining nucleotides 1552 of NUP98 to nucleotide 3506 of NSD1. The reciprocal transcript fuses NSD1 and NUP98 mRNA in-frame joining nucleotide 3505 of NSD1 to nucleotide 1553 of NUP98.
Detection RT-PCR with sense NUP98-5 (5'-TCTTGGTACAGGAGCCTTTG-3', and antisense NSD1-1 (5'TCCAAAAGCCACTTGCTTGGC-3') primers
Fusion Protein

To be noted

Additional cases are needed to delineate the epidemiology of this rare entity:
you are welcome to submit a paper to our new Case Report section.


Potential role for DNA topoisomerase II poisons in the generation of t(11;20)(p15;q11) translocations.
Ahuja HG, Felix CA, Aplan PD
Genes, chromosomes & cancer. 2000 ; 29 (2) : 96-105.
PMID 10959088
A cryptic t(5;11)(q35;p15.5) in 2 children with acute myeloid leukemia with apparently normal karyotypes, identified by a multiplex fluorescence in situ hybridization telomere assay.
Brown J, Jawad M, Twigg SR, Saracoglu K, Sauerbrey A, Thomas AE, Eils R, Harbott J, Kearney L
Blood. 2002 ; 99 (7) : 2526-2531.
PMID 11895789
Subtelomeric chromosome rearrangements are detected using an innovative 12-color FISH assay (M-TEL).
Brown J, Saracoglu K, Uhrig S, Speicher MR, Eils R, Kearney L
Nature medicine. 2001 ; 7 (4) : 497-501.
PMID 11283680
Two distinct nuclear receptor interaction domains in NSD1, a novel SET protein that exhibits characteristics of both corepressors and coactivators.
Huang N, vom Baur E, Garnier JM, Lerouge T, Vonesch JL, Lutz Y, Chambon P, Losson R
The EMBO journal. 1998 ; 17 (12) : 3398-3412.
PMID 9628876
A novel gene, NSD1, is fused to NUP98 in the t(5;11)(q35;p15.5) in de novo childhood acute myeloid leukemia.
Jaju RJ, Fidler C, Haas OA, Strickson AJ, Watkins F, Clark K, Cross NC, Cheng JF, Aplan PD, Kearney L, Boultwood J, Wainscoat JS
Blood. 2001 ; 98 (4) : 1264-1267.
PMID 11493482
A new recurrent translocation, t(5;11)(q35;p15.5), associated with del(5q) in childhood acute myeloid leukemia. The UK Cancer Cytogenetics Group (UKCCG)
Jaju RJ, Haas OA, Neat M, Harbott J, Saha V, Boultwood J, Brown JM, Pirc-Danoewinata H, Krings BW, Müller U, Morris SW, Wainscoat JS, Kearney L
Blood. 1999 ; 94 (2) : 773-780.
PMID 10397745
An optimized set of human telomere clones for studying telomere integrity and architecture.
Knight SJ, Lese CM, Precht KS, Kuc J, Ning Y, Lucas S, Regan R, Brenan M, Nicod A, Lawrie NM, Cardy DL, Nguyen H, Hudson TJ, Riethman HC, Ledbetter DH, Flint J
American journal of human genetics. 2000 ; 67 (2) : 320-332.
PMID 10869233
Molecular characterization of NSD1, a human homologue of the mouse Nsd1 gene.
Kurotaki N, Harada N, Yoshiura K, Sugano S, Niikawa N, Matsumoto N
Gene. 2001 ; 279 (2) : 197-204.
PMID 11733144
NUP98 gene fusions in hematologic malignancies.
Lam DH, Aplan PD
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2001 ; 15 (11) : 1689-1695.
PMID 11681408


This paper should be referenced as such :
Kearney, L
Atlas Genet Cytogenet Oncol Haematol. 2002;6(3):209-211.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Translocations implicated (Data extracted from papers in the Atlas)

 t(5;11)(q35;p15.5) NUP98/NSD1

External links

NUP98 (11p15.4) NSD1 (5q35.2)

NUP98 (11p15.4) NSD1 (5q35.2)

NUP98 (11p15.4) NSD1 (5q35.2)

Mitelman databaset(5;11)(q35;p15.5) [Case List]    t(5;11)(q35;p15.5) [Transloc-MCList] NUP98/NSD1 [Fusion-MCList]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9861/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
Mitelman databaseNUP98/NSD1 [MCList]  NUP98 (11p15.4) NSD1 (5q35.2)
TCGA_FusionNUP98/NSD1 [LAML]  NUP98 (11p15.4) NSD1 (5q35.2)
TICdbNUP98/NSD1  NUP98 (11p15.4) NSD1 (5q35.2)
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