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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
  

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

Genes ALK ALK ATIC DGKA

Translocations implicated (Data extracted from papers in the Atlas)

 t(2;5)(p23;q35) NPM1/ALK

External links

Mitelman database Mitelman database (CGAP - NCBI)
t(2;5)(p23;q35) - Mitelman database (CGAP - NCBI)

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)
Atlas Genet Cytogenet Oncol Haematol. 2001;5(4):283-285.
Free online version   Free pdf version   [Bibliographic record ]
Atlas Genet Cytogenet Oncol Haematol. December 1997
http://documents.irevues.inist.fr/bitstream/handle/2042/32068/12-1997-t0205.pdf
URL : http://AtlasGeneticsOncology.org/Anomalies/t0205.html

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