Molecular detection of the (2;5) translocation of non-Hodgkin's lymphoma by reverse transcriptase-polymerase chain reaction.
The t(2;5)(p23;q35) translocation was initially identified in cases of anaplastic large-cell lymphoma (ALCL) that expressed the Ki-1 (CD30) antigen. We have recently cloned this translocation and shown it to encode a chimeric product consisting of the N-terminal portion of a nonribosomal nucleolar phosphoprotein, nucleophosmin (NPM), from chromosome 5, fused to the kinase domain of a novel transmembrane tyrosine-specific protein kinase, anaplastic lymphoma kinase (ALK), from chromosome 2. To better define the spectrum of lymphomas that contain this translocation, we have analyzed 70 cases of non-Hodgkin's lymphoma (NHL) for expression of the t(2;5)-derived NPM/ALK chimeric message by reverse transcriptase-polymerase chain reaction (RT-PCR). Using a previously described set of oligonucleotide primers, NPM/ALK chimeric transcripts were detected in 21 of 22 cases that contained the t(2;5) by cytogenetic analysis and in 10 of 48 cases that either lacked evidence of the t(2;5) or had unsuccessful cytogenetics. In all but 1 case, the NPM/ALK PCR products were of identical size and sequence, suggesting that the genomic chromosome breaks are clustered in a single intron in both NPM and ALK. The NPM/ALK-expressing cases were not confined to NHLs with anaplastic morphology and included 15 ALCLs, 6 immunoblastic lymphomas, and 10 diffuse large-cell lymphomas. Moreover, only slightly greater than half of the cases with anaplastic morphology and 59% of CD30-expressing cases were NPM/ALK positive. Thus, neither anaplastic morphology nor the expression of CD30 accurately predicted the presence of this molecular genetic subtype of lymphoma.
Downing
J R
JR
Department of Pathology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Shurtleff
S A
SA
Zielenska
M
M
Curcio-Brint
A M
AM
Behm
F G
FG
Head
D R
DR
Sandlund
J T
JT
Weisenburger
D D
DD
Kossakowska
A E
AE
Thorner
P
P
D000328:Adult; D001483:Base Sequence; D002648:Child; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D005819:Genetic Markers; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics*; D000090243:Nucleophosmin; D016133:Polymerase Chain Reaction; D014178:Translocation, Genetic / Q000235:genetics
D005819:Genetic Markers; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin