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t(4;11)(q21;p15) NUP98/RAP1GDS1

Written2002-07Franck Viguié
Laboratoire de Cytogenetique - Service d'Hematologie Biologique, Hopital Hotel-Dieu - 75181 Paris Cedex 04, France

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho 9837/3 T lymphoblastic leukaemia/lymphoma
Atlas_Id 1473
Note The breakpoint on chromosome 4 must be relocated in 4q23, since RAP1GDS1 gene maps at 4q23, see the complete update of this paper at t(4;11)(q23;p15) ..
 
  t(4;11)(q21;p15) G- banding - Courtesy Diane H. Norback, Eric B. Johnson, Sara Morrison-Delap Cytogenetics at the Waisman Center

Clinics and Pathology

Disease T-cell acute lymphoblastic leukemia.
Phenotype / cell stem origin Lymphoblasts, either L1 or L2 in the FAB classification; mature T and myeloid markers variably co-expressed.
Epidemiology Rare, approximately 10 cases described; evaluated to 2-5% of adult T-ALL ; not evaluated in childhood ALL; both sexes equally involved; found in children or young adults.
Clinics No notable particular aspect.
Prognosis Probably unfavorable, median survival below 18 months; improved by allogeneic bone marrow transplantation.

Cytogenetics

Cytogenetics Morphological In approximately 2/3 of cases; 2 cases with del(12p).
Cytogenetics Molecular Two BAC clones 290A12 and 118H17 (California Institute of Technology BAC library) encompasses all NUP98 gene and are split by translocation.
Variants Not described.

Genes involved and Proteins

Gene Name RAP1GDS1
Location 4q22.3
Protein smgGDS, 558 amino acids; stimulates GDP --> GTP transition in a series of small GTP-binding proteins (g proteins) including rap1a, rap1b, K-ras, rac1, rac2, rhoA and ralB.
Somatic mutations Not involved in other known clonal rearrangement associated with tumoral proliferation.
Gene Name NUP98
Location 11p15.4
Protein Nucleoporin 98, a 98 kDa component of the nuclear pore complex implicated in nucleo-cytoplasmic transport.
Somatic mutations Involved in different types of acute myeloid leukemia, as fusion gene with HOX A9, DDX10, HOX D13, TOP1, PMX1 and LEDGF, resulting respectively from t(7;11)(p15;p15), inv(11)(p15q22), t(2;11)(q31;p15), t(11;20)(p15;q11), t(1;11)(q23;p15) and t(9;11)(p22;p15).

Result of the chromosomal anomaly

Hybrid gene
Description NUP98 breakpoint in the intron between exons B and C; 5'-part of NUP98 is fused in frame with the whole coding sequence of RAP1GDS1; fusion gene called NRG: 5'-NUP-RAP1GDS1-3'. Variant described with breakpoint in NUP98 before exon A.
  
Fusion Protein
Description t(4;11) generates only one chimeric protein 5'NUP98 -3'RAP1GDS1 which contains a variable part of NUP98 and the totality of smgGDS except for the initial methionine.
  

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

Molecular evaluation of the NUP98/RAP1GDS1 gene frequency in adults with T-acute lymphoblastic leukemia.
Cimino G, Sprovieri T, Rapanotti MC, Foá R, Mecucci C, Mandelli F
Haematologica. 2001 ; 86 (4) : 436-437.
PMID 11325654
 
The (4;11)(q21;p15) translocation fuses the NUP98 and RAP1GDS1 genes and is recurrent in T-cell acute lymphocytic leukemia.
Hussey DJ, Nicola M, Moore S, Peters GB, Dobrovic A
Blood. 1999 ; 94 (6) : 2072-2079.
PMID 10477737
 
Mapping of the chromosome 11 breakpoint of the t(4;11)(q21;p14-15) translocation.
Kalatzis V, Peters GB, Dobrovic A
Cancer genetics and cytogenetics. 1993 ; 69 (2) : 122-125.
PMID 8402548
 
t(4;11)(q21;p15) translocation involving NUP98 and RAP1GDS1 genes: characterization of a new subset of T acute lymphoblastic leukaemia.
Mecucci C, La Starza R, Negrini M, Sabbioni S, Crescenzi B, Leoni P, Di Raimondo F, Krampera M, Cimino G, Tafuri A, Cuneo A, Vitale A, Foà R
British journal of haematology. 2000 ; 109 (4) : 788-793.
PMID 10929031
 

Citation

This paper should be referenced as such :
Viguié, F
t(4;11)(q21;p15)
Atlas Genet Cytogenet Oncol Haematol. 2002;6(4):301-302.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Anomalies/t0411q21p15ID1473.html


Translocations implicated (Data extracted from papers in the Atlas)

 t(4;11)(q21;p15) NUP98/RAP1GDS1

External links

NUP98 (11p15.4) RAP1GDS1 (4q23)

NUP98 (11p15.4) RAP1GDS1 (4q23)

Mitelman databaset(4;11)(q21;p15) [Case List]    t(4;11)(q21;p15) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9837/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
Mitelman databaseNUP98/RAP1GDS1 [MCList]  NUP98 (11p15.4) RAP1GDS1 (4q23)
TICdbNUP98/RAP1GDS1  NUP98 (11p15.4) RAP1GDS1 (4q23)
 
Disease databaset(4;11)(q21;p15) NUP98/RAP1GDS1
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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