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t(11;12)(p15;p13) NUP98::KDM5A

Written2013-01Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
This article is an update of :
2006-04Laura JCM van Zutven, H Berna Beverloo
Department of Clinical Genetics, Erasmus MC, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands

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ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
Atlas_Id 1428

Clinics and Pathology

Disease Acute megakaryoblastic leukemia (AML -M7)
Note Acute megakaryoblastic leukemia (AMKL) was so far divided into three subgroups: AMKL arising in patients with Down syndrome (DS-AMKL), AMKL with a t(1;22)(p13;q13) giving rise of a 5' OTT - 3' MAL fusion gene, and "other" AMLKs, non Down syndrome / non t(1;22).
Two new categories have recently been individualized from the subgroup "non Down syndrome / non t(1;22)": the inv(16)(p13q24) CBFA2T3/GLIS2, and the t(11;12)(p15;p13) NUP98/KDM5A (Gruber et al., 2012; Thiollier et al., 2012). This t(11;12)(p15;p13) has been described earlier in a single case (van Zutven et al., 2006).
Epidemiology From the two recent studies, t(11;12)(p15;p13) NUP98/KDM5A was found in about 10% of pediatric acute megakaryoblastic leukemia, excluding AMLKs occuring in Down syndrome patients; NUP98/KDM5A was detected in 8% (4 of 48) of pediatric cases. This chimeric transcript was not detected in adult AMKLs (Gruber et al., 2012). From another validation cohort of 22 non-DS pediatric AMKL, 9 DS AMKL, and 8 adult AMKL, a NUP98/KDM5A fusion was characterized in two patients (Thiollier et al., 2012).
Clinics 7 cases to date; data on age and sex are available in 5 cases (van Zutven et al., 2006; Gruber et al., 2012): there was 5 boys and no girl; sex ratio, so far, appears to be highly unbalanced, although the sample is very small; median age was 1 year 4 months (range: 1 year - 4 years).
Prognosis Prognostic data available in only one case (van Zutven et al., 2006) : the patient remained in complete remission for at least 5 years.


Cytogenetics Morphological Not visible with conventional banding techniques alone: misdiagnosed as add(11)(p15) and der(21)(t(11;21)(p15;p13), and chromosome 12 was cytogenetically normal by conventional banding techniques and only identified as a partner in this translocation after FISH in the first reported case (van Zutven et al., 2006). A complex karyotype was found in 4 of the 5 cases with data on chromosomes; the remaining case exhibited an apparently normal karyotype (van Zutven et al., 2006; Gruber et al., 2012).

Genes involved and Proteins

Gene NameNUP98 (nucleoporin 98 kDa)
Location 11p15.4
Protein 920 amino acids; 97 kDa; contains repeated motifs (GLFG and FG) in N-term and a RNA binding motif in C-term. Nucleoporin: associated with the nuclear pore complex; role in nucleocytoplasmic transport processes.
Gene NameKDM5A (Jumonji, AT rich interactive domain 1A (RBBP2-like))
Location 12p13.33
Note The gene was previously known as JARID1A.
Protein 1722 amino acids; 196 kD; retinoblastoma binding protein 2. Lysine-specific histone 3 demethylase; involved in chromatin-regulation; can function as a transcriptional repressor. KDM5A-mediated histone H3 lysine 4 demethylation contributes to silencing of retinoblastoma target genes (Chicas et al., 2012). Dysregulation of KDM5A is associated with various human cancers: gastric cancer, lung cancer, breast cancer (Hou et al., 2012).

Result of the chromosomal anomaly

Hybrid gene
Description In-frame fusion of the first 13 exons of NUP98 to exons 28-31 of KDM5A.
Transcript 5' NUP98 - 3' KDM5A.
Detection FISH: BAC clones RP11-348A20 (NUP98) and RP11-283I3 (spanning KDM5A exon 11-31) colocalize.
Fusion Protein
  Schematic representation of the fusion NUP98-KDM5A (previously named NUP98-JARID1A). From up to down: NUP98, JARID1A and the putative chimeric NUP98-JARID1A structure. FG-repeats: phenylalanine-glycine repeats; JMJ: Jumonji domains; ARID: AT-rich interaction domain; PHD: plant homeodomain fingers or LAP domains. The arrow indicates the position of the fusion (Laura JCM van Zutven and H Berna Beverloo).
Description The NUP98/KDM5A fusion protein contains the Phe-Gly (FG) repeats of the N-terminal part of NUP98. The KDM5A (JARID1A) sequence starting with exon 28 still contains the sequence encoding the C-terminal PHD domain.
Oncogenesis Results in deregulation of HOXA genes through recruitment of the histone acetyltransferase CBP/p300 (Thiollier et al., 2012).

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.


H3K4 demethylation by Jarid1a and Jarid1b contributes to retinoblastoma-mediated gene silencing during cellular senescence.
Chicas A, Kapoor A, Wang X, Aksoy O, Evertts AG, Zhang MQ, Garcia BA, Bernstein E, Lowe SW.
Proc Natl Acad Sci U S A. 2012 Jun 5;109(23):8971-6. doi: 10.1073/pnas.1119836109. Epub 2012 May 21.
PMID 22615382
An Inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryoblastic leukemia.
Gruber TA, Larson Gedman A, Zhang J, Koss CS, Marada S, Ta HQ, Chen SC, Su X, Ogden SK, Dang J, Wu G, Gupta V, Andersson AK, Pounds S, Shi L, Easton J, Barbato MI, Mulder HL, Manne J, Wang J, Rusch M, Ranade S, Ganti R, Parker M, Ma J, Radtke I, Ding L, Cazzaniga G, Biondi A, Kornblau SM, Ravandi F, Kantarjian H, Nimer SD, Dohner K, Dohner H, Ley TJ, Ballerini P, Shurtleff S, Tomizawa D, Adachi S, Hayashi Y, Tawa A, Shih LY, Liang DC, Rubnitz JE, Pui CH, Mardis ER, Wilson RK, Downing JR.
Cancer Cell. 2012 Nov 13;22(5):683-97. doi: 10.1016/j.ccr.2012.10.007.
PMID 23153540
Genomic amplification and a role in drug-resistance for the KDM5A histone demethylase in breast cancer.
Hou J, Wu J, Dombkowski A, Zhang K, Holowatyj A, Boerner JL, Yang ZQ.
Am J Transl Res. 2012;4(3):247-56. Epub 2012 Jul 22.
PMID 22937203
Characterization of novel genomic alterations and therapeutic approaches using acute megakaryoblastic leukemia xenograft models.
Thiollier C, Lopez CK, Gerby B, Ignacimouttou C, Poglio S, Duffourd Y, Guegan J, Rivera-Munoz P, Bluteau O, Mabialah V, Diop M, Wen Q, Petit A, Bauchet AL, Reinhardt D, Bornhauser B, Gautheret D, Lecluse Y, Landman-Parker J, Radford I, Vainchenker W, Dastugue N, de Botton S, Dessen P, Bourquin JP, Crispino JD, Ballerini P, Bernard OA, Pflumio F, Mercher T.
J Exp Med. 2012 Oct 22;209(11):2017-31. doi: 10.1084/jem.20121343. Epub 2012 Oct 8.
PMID 23045605
Identification of NUP98 abnormalities in acute leukemia: JARID1A (12p13) as a new partner gene.
van Zutven LJ, Onen E, Velthuizen SC, van Drunen E, von Bergh AR, van den Heuvel-Eibrink MM, Veronese A, Mecucci C, Negrini M, de Greef GE, Beverloo HB.
Genes Chromosomes Cancer. 2006 May;45(5):437-46.
PMID 16419055


This paper should be referenced as such :
Huret, JL
t(11;12)(p15;p13) NUP98/KDM5A
Atlas Genet Cytogenet Oncol Haematol. 2013;17(6):430-432.
Free journal version : [ pdf ]   [ DOI ]
On line version :
History of this paper:
van Zutven, LJCM ; Beverloo, HB. t(11;12)(p15;p13). Atlas Genet Cytogenet Oncol Haematol. 2006;10(4):259-260.

Other genes implicated (Data extracted from papers in the Atlas) [ 1 ]

Genes KDM5A

Translocations implicated (Data extracted from papers in the Atlas)

 t(11;12)(p15;p13) NUP98/KDM5A

External links

NUP98 (11p15.4) KDM5A (12p13.33)

NUP98 (11p15.4) KDM5A (12p13.33)

Mitelman databaset(11;12)(p15;p13)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9861/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
Mitelman databaseNUP98::KDM5A [MCList]  NUP98 (11p15.4) KDM5A (12p13.33)
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