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t(2;5)(p23;q35) NPM1/ALK

Identity

 
  t(2;5)(p23;q35) G-banding (left), and R- banding (right); note tetraploid cells (left middle and bottom) -Courtesy Jean-Luc Lai and Alain Vanderhaegen

Clinics and Pathology

Disease Translocations involving 2p23 are found in more than half cases of anaplasic large cell lymphoma (ALCL), a high grade non Hodgkin lymphoma (NHL). They involve ALK, and are therefore called ALK+ ALCL. The t(2;5) is the far most frequent 2p23 translocation in ALK+ ALCL.
Phenotype / cell stem origin T-cell in 80% (or 100%?), oær null-cell type; B-cell cases, if they exist, would represent cases of large B-cell lymphomas; CD30+; present with some overlapping features with Hodgkin's disease: CD30 positivity and Reed-Sternberg like cells, but the t(2;5) is not found in Hodgkin's disease (it has long been debated)
Epidemiology 10% of NHL; found in children and young adults; median around 16 yrs)
Clinics involve lymph nodes and extra nodal sites such as lungs and gastro intestinal tract
Cytology t(2;5) is found in about 30-50% of anaplastic large cell NHL (also called ALCL); it was thought previously that the t(2;5) could be found in diffuse large cell NHL or immunoblastic NHL; however, cases may easily be misdiagnosed, as the malignant cells display a pleomorphic appearance
Prognosis although t(2;5) is found in aggressive high grade tumours, a 80% five yr survival seems to be associated with this anomaly

Cytogenetics

Additional anomalies sole anomaly in less than 20% of cases; often part of a complex karyotype, with various structural and/or numerical anomalies; recurrent numerical anomalies are: +7, found in 20% of cases, +9, and +X, in 5 to 10% of cases.
Variants closely related anomalies, also found in anaplastic large cell lymphoma, are: t(X;2)(q11;p23), t(1;2)(q25;p23), inv(2)(p23q35), t(2;3)(p23;q21), t(2;17)(p23;q23), t(2;19)(p23; p13.1) and t(2;22)(p23;q11.2). They all involve ALK in 2p23.

Genes involved and Proteins

Gene Name ALK
Location 2p23
Protein after glycosylation, produces a glycoprotein; membrane associated tyrosine kinase receptor
Gene Name NPM1
Location 5q35
Protein nuclear localisation; RNA binding nucleolar phosphoprotein involved in preribosomal assembly

Result of the chromosomal anomaly

Hybrid gene
Description 5' NPM-3' ALK on der(5)
Transcript 2.4 kb
  
Fusion Protein
Description 80 kDa; 680 amino acids; the 116 N-term aminoacids from NPM are fused to the 563 C-term ¾aminoacids of ALK (i.e. composed of the oligomerization domain and the metal binding site of NPM1, and the entire cytoplasmic portion of ALK); no apparent expression of the ALK/NPM1 counterpart. Characteristic localisation both in the cytoplasm and in the nucleus, due to heterooligomerization of NPM-ALK and normal NPM whereas the normal NPM protein is confined to the nucleus; constitutive activation of the catalytic domain of ALK.
Expression Localisation localisation: both in the cytoplasm and in the nucleus (nucleoplasm and nucleolus)
Oncogenesis via the kinase function activated by oligomerization of NPM-ALK mediated by the NPM part
  

External links

Other databaset(2;5)(p23;q35) NPM1/ALK Mitelman database (CGAP - NCBI)

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

Genes ALK ALK ATIC

Bibliography

CD30-positive large cell lymphomas ('Ki-1 lymphoma') are associated with a chromosomal translocation involving 5q35.
Mason DY, Bastard C, Rimokh R, Dastugue N, Huret JL, Kristoffersson U, Magaud JP, Nezelof C, Tilly H, Vannier JP
British journal of haematology. 1990 ; 74 (2) : 161-168.
PMID 2156548
 
Analysis of the t(2;5)(p23;q35) translocation by reverse transcription-polymerase chain reaction in CD30+ anaplastic large-cell lymphomas, in other non-Hodgkin's lymphomas of T-cell phenotype, and in Hodgkin's disease.
Wellmann A, Otsuki T, Vogelbruch M, Clark HM, Jaffe ES, Raffeld M
Blood. 1995 ; 86 (6) : 2321-2328.
PMID 7662979
 
Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma.
Morris SW, Kirstein MN, Valentine MB, Dittmer KG, Shapiro DN, Saltman DL, Look AT
Science (New York, N.Y.). 1994 ; 263 (5151) : 1281-1284.
PMID 8122112
 
Cytogenetics of lymphomas: a brief review of its theoretical and practical significance.
Donner LR
Cancer genetics and cytogenetics. 1997 ; 94 (1) : 20-26.
PMID 9078287
 
Role of the nucleophosmin (NPM) portion of the non-Hodgkin's lymphoma-associated NPM-anaplastic lymphoma kinase fusion protein in oncogenesis.
Bischof D, Pulford K, Mason DY, Morris SW
Molecular and cellular biology. 1997 ; 17 (4) : 2312-2325.
PMID 9121481
 
CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features.
Stein H, Foss HD, Dˆºrkop H, Marafioti T, Delsol G, Pulford K, Pileri S, Falini B
Blood. 2000 ; 96 (12) : 3681-3695.
PMID 11090048
 
CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features.
Stein H, Foss HD, Dˆºrkop H, Marafioti T, Delsol G, Pulford K, Pileri S, Falini B
Blood. 2000 ; 96 (12) : 3681-3695.
PMID 11090048
 
CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features.
Stein H, Foss HD, Dˆºrkop H, Marafioti T, Delsol G, Pulford K, Pileri S, Falini B
Blood. 2000 ; 96 (12) : 3681-3695.
PMID 11090048
 
Alk+ CD30+ lymphomas: a distinct molecular genetic subtype of non-Hodgkin's lymphoma.
Morris SW, Xue L, Ma Z, Kinney MC
British journal of haematology. 2001 ; 113 (2) : 275-295.
PMID 11380391
 
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed

Contributor(s)

Written12-1997Jean-Loup Huret
Updated08-2001Jean-Loup Huret

Citation

This paper should be referenced as such :
Huret JL . t(2;5)(p23;q35) NPM1/ALK. Atlas Genet Cytogenet Oncol Haematol. December 1997 .
Huret JL . t(2;5)(p23;q35) NPM1/ALK. Atlas Genet Cytogenet Oncol Haematol. August 2001 .
URL : http://AtlasGeneticsOncology.org/Anomalies/t0205.html

The various updated versions of this paper are referenced and archived by INIST as such :
http://documents.irevues.inist.fr/bitstream/handle/2042/32068/12-1997-t0205.pdf   [ Bibliographic record ]
http://documents.irevues.inist.fr/bitstream/2042/37790/1/08-2001-t0205.pdf   [ Bibliographic record ]

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indexed on : Fri Apr 18 14:11:00 CEST 2014


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