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

2001-08-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

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 stem cell origin

T-cell in 80% (or 100%?), or null-cell type; B-cell cases, if they exist, would represent cases of large B-cell lymphomas; CD30+; present with some overlapping features with Hodgkins disease: CD30 positivity and Reed-Sternberg like cells, but the t(2;5) is not found in Hodgkins 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 (anaplastic lymphoma receptor tyrosine kinase)
Location
2p23.2
Protein description
after glycosylation, produces a glycoprotein; membrane associated tyrosine kinase receptor
Gene name
NPM1 (nucleophosmin)
Location
5q35.1
Protein description
nuclear localisation; RNA binding nucleolar phosphoprotein involved in preribosomal assembly

Result of the Chromosomal Anomaly

Description

5 NPM-3 ALK on der(5)

Transcript

2.4 kb

Description

80 kDa; 680 amino acids; the 116 N-term aminoacids from NPM are fused to the 563 C-term aminoacids 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

Bibliography

Pubmed IDLast YearTitleAuthors
91214811997Role of the nucleophosmin (NPM) portion of the non-Hodgkin's lymphoma-associated NPM-anaplastic lymphoma kinase fusion protein in oncogenesis.Bischof D et al
90782871997Cytogenetics of lymphomas: a brief review of its theoretical and practical significance.Donner LR et al
21565481990CD30-positive large cell lymphomas ('Ki-1 lymphoma') are associated with a chromosomal translocation involving 5q35.Mason DY et al
81221121994Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma.Morris SW et al
113803912001Alk+ CD30+ lymphomas: a distinct molecular genetic subtype of non-Hodgkin's lymphoma.Morris SW et al
110900482000CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features.Stein H et al
76629791995Analysis 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 et al

Summary

Fusion gene

NPM1/ALK NPM1 (5q35.1) ALK (2p23.2) COF 198 199 200 201 420 448 449 450 451 452 453 454 455 456 457 458|NPM1/ALK NPM1 (5q35.1) ALK (2p23.2) M ins(5;2)(q35;p23p23) t(2;5)(p23;q35)|NPM1/ALK NPM1 (5q35.1) ALK (2p23.2) TIC
Atlas Image
t(2;5)(p23;q35) NPM1/ALK G-banding (left) [note tetraploid cells (second and third row)] and R- banding (right); - Courtesy Jean-Luc Lai and Alain Vanderhaegen; center: G-banding - Courtesy Adriana Zamecnikova. Fluorescence in situ hybridization (FISH) with Vysis ALK Break Apart probe (Abbott Molecular, US) showing rearrangement of the gene on metaphases with t(2;5)(p23;q35) (green signal on der(2) and red signal on der(5) chromosome). - Courtesy Adriana Zamecnikova.

Citation

Jean-Loup Huret

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

Atlas Genet Cytogenet Oncol Haematol. 2001-08-01

Online version: http://atlasgeneticsoncology.org/haematological/2000/t(2;5)(p23;q35)

Historical Card

1997-12-01 t(2;5)(p23;q35) NPM1/ALK by  Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

1997-08-01 t(2;5)(p23;q35) NPM1/ALK by  Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

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