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

2002-07-01   Franck Viguié 

Clinics and Pathology

Disease

T-cell acute lymphoblastic leukemia.

Phenotype stem cell 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 (RAP1, GTP-GDP dissociation stimulator 1)
Location
4q23
Protein description
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 (nucleoporin 98 kDa)
Location
11p15.4
Protein description
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

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.t(4;11) generates only one chimeric protein 5NUP98 -3RAP1GDS1 which contains a variable part of NUP98 and the totality of smgGDS except for the initial methionine.

Bibliography

Pubmed IDLast YearTitleAuthors
113256542001Molecular evaluation of the NUP98/RAP1GDS1 gene frequency in adults with T-acute lymphoblastic leukemia.Cimino G et al
104777371999The (4;11)(q21;p15) translocation fuses the NUP98 and RAP1GDS1 genes and is recurrent in T-cell acute lymphocytic leukemia.Hussey DJ et al
84025481993Mapping of the chromosome 11 breakpoint of the t(4;11)(q21;p14-15) translocation.Kalatzis V et al
109290312000t(4;11)(q21;p15) translocation involving NUP98 and RAP1GDS1 genes: characterization of a new subset of T acute lymphoblastic leukaemia.Mecucci C et al

Summary

Fusion gene

NUP98/RAP1GDS1 NUP98 (11p15.4) RAP1GDS1 (4q23) M t(4;11)(q23;p15)|NUP98/RAP1GDS1 NUP98 (11p15.4) RAP1GDS1 (4q23) TIC

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) ..
Atlas Image
t(4;11)(q21;p15) G- banding - Courtesy Diane H. Norback, Eric B. Johnson, Sara Morrison-Delap Cytogenetics at the Waisman Center

Citation

Franck Viguié

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

Atlas Genet Cytogenet Oncol Haematol. 2002-07-01

Online version: http://atlasgeneticsoncology.org/haematological/1473/t(4;11)(q21;p15)

External Links