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Molecular detection of the (2;5) translocation of non-Hodgkin's lymphoma by
reverse transcriptase-polymerase chain reaction
JR Downing, SA Shurtleff, M Zielenska, AM Curcio-Brint, FG Behm, DR Head, JT Sandlund, DD Weisenburger, AE Kossakowska and P Thorner
Department of Pathology, St Jude Children's Research Hospital, Memphis, TN
38105, USA.
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.
Volume 85,
Issue 12,
pp. 3416-3422,
06/15/1995
Copyright © 1995 by The American Society of Hematology
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