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t(X;11)(q28;p15) NUP98/HMGB3

Written2017-03Tatiana Gindina
R.M. Gorbacheva Research Institute of Pediatric Oncology Hematology and Transplantation at First Saint-Petersburg State Medical University named I.P.Pavlov, Saint-Petersburg, Russia / tatgindina@gmail.com

Abstract Review on t(X;11)(q28;p15), with data on the genes involved

Keywords Chromosome X; Chromosome 11; Acute myelomonocytic leukaemia

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424
ICD-Morpho 9920/3 Therapy-related myeloid neoplasms
ICD-Morpho 9867/3 Acute myelomonocytic leukaemia
Atlas_Id 1588

Clinics and Pathology

Disease Therapy-related acute myeloid leukemia ( M4 AML)
Epidemiology Only one case to date: a 73-year-old female patient.

Cytogenetics

Cytogenetics Morphological It is a semi-cryptic translocation, not visible with conventional cytogenetics alone and identified as a partner in the translocation after FISH technique with the NUP98 probe and the telomeric probe RP11-479B17 in the first reported case (Romana et al, 2006).
Additional anomalies The patient showed a complex karyotype with a t(5;12)(q11;p13) as the only one chromosomal aberration observed in the stemline and a der(11) chromosome in two sidelines. (Romana et al, 2006).

Genes involved and Proteins

Gene NameHMGB3 (high mobility group box 3)
Location Xq28
Protein HMGB3 encodes a member of a family of proteins containing one or more high mobility group (HMG) DNA-binding motifs. The protein plays an important role in maintaining stem cell populations, and may be aberrantly expressed in tumor cells.
Gene NameNUP98 (nucleoporin 98 kDa)
Location 11p15.4
Protein NUP98 belongs to the nucleoporin gene family and encodes a 186 kDa precursor protein that undergoes autoproteolytic cleavage to produce a 98 kDa nucleoporin and 96 kDa nucleoporin. The 98 kDa nucleoporin contains a Gly-Leu-Phe-Gly (GLGF) repeat domain and participates in many cellular processes including nuclear import/export, mitotic progression, and regulation of gene expression. The 96 kDa nucleoporin is a component of the nuclear pore complex.

Result of the chromosomal anomaly

Hybrid gene
Note 5' NUP98 - 3' HMGB3
Description Nucleotide sequence analyses revealed an in-frame fusion of the exon 11 of NUP98 to the exon 2 of HMGB3. No reciprocal HMGB3-NUP98 transcript could be detected (Petit et al, 2010).
  
Fusion Protein
 
  Schematic representation of the NUP98/HMGB3 chimeric transcript, the native and chimeric proteins, showing the Gly-Leu-Phe-Gly (GLFG) repeats and RNA binding domain of NUP98 and the two high mobility group (HMG) boxes of HMGB3.
Description The NUP98-HMGB3 protein is composed of the first 422 amino acids of NUP98 fused to the entire HMGB3 coding sequence (Petit et al, 2010).
Oncogenesis The NUP98-fusion proteins induce leukemic transformation through the upregulation of HOXA genes and the Hox cofactor MEIS1. However, in mouse model, it has been shown the NUP98/HMGB3-expressing blasts upregulate HOXA9 only weakly and retain wild-type levels of MEIS1. Evidently, the transformation mediated by the NUP98/HMGB3 fusion does not involve deregulated activity of the canonical HOXA - MEIS1 pathway. The ectopic expression of HMGB3, as a result of the fusion with NUP98, can bypass the requirement of a concomitant HOXA9 and MEIS1 misregulation in human malignancy. It seems that the several transformation pathways might be involved in the leukemogenic properties of NUP98 fusions. NUP98/HMGB3 is the first example of a NUP98 leukemogenic fusion whose expression is not associated with a strong HOXA and concomitant MEIS1 expression (Petit et al, 2010).
  

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.

Bibliography

NUP98-HMGB3: a novel oncogenic fusion.
Petit A, Ragu C, Della-Valle V, et al.
Leukemia. 2010; 24(3):654-658
PMID 19956199
 
NUP98 rearrangements in hematopoietic malignancies: a study of the Groupe Francophone de Cytogenetique Hematologique.
Romana SP, Radford-Weiss I, Ben Abdelali R, et al.
Leukemia. 2006; 20(4):696-706
PMID 16467868
 

Citation

This paper should be referenced as such :
Gindina T
t(X;11)(q28;p15) NUP98/HMGB3;
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Anomalies/t0X11q28p15ID1588.html


Translocations implicated (Data extracted from papers in the Atlas)

 t(X;11)(q28;p15) NUP98/HMGB3

External links

Mitelman databaset(X;11)(q28;p15) [Case List]    t(X;11)(q28;p15) [Association List] Mitelman database (CGAP - NCBI)
arrayMapMorph ( 9920/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapMorph ( 9867/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
 
Disease databaset(X;11)(q28;p15) NUP98/HMGB3
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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