| Written | 2002-07 | Franck Viguié |
| Laboratoire de Cytogenetique - Service d'Hematologie Biologique, Hopital Hotel-Dieu - 75181 Paris Cedex 04, France |
| 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 (RAP1, GTP-GDP dissociation stimulator 1) |
| Location | 4q23 |
| 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 (nucleoporin 98 kDa) |
| 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 |
| 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. |
| 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 |
| REVIEW articles | automatic search in PubMed |
| Last year articles | automatic search in PubMed |
| All articles | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Mon Jul 9 10:11:38 CEST 2018 |
For comments and suggestions or contributions, please contact us