Lack of the t(2;5) or other mutations resulting in expression of anaplastic lymphoma kinase catalytic domain in CD30+ primary cutaneous lymphoproliferative disorders and Hodgkin's disease.
The t(2;5) (p23;q35) chromosomal translocation has been found in a high proportion of lymph node-based CD30+ large cell lymphomas of T-cell lineage. This translocation is believed to result in the expression of a fusion protein containing the catalytic domain of anaplastic lymphoma kinase (ALK) under the control of the promoter for nucleophosmin, a nucleolar phosphoprotein. Expression of ALK activity, which does not normally occur in lymphocytes, is postulated to be involved in the pathogenesis of lymphomas bearing the t(2;5) translocation. Several primary cutaneous lymphoproliferative disorders and Hodgkin's disease are also known to contain CD30+ large lymphoid cells. To determine the role of the t(2;5) translocation in these diseases, we developed a DNA-based polymerase chain reaction (PCR)/Southern blot assay to detect this translocation at the genomic level in lymphomatoid papulosis (14 cases), primary cutaneous CD30+ large cell lymphoma of T-lineage (10 cases) and Hodgkin's disease (13 cases). Two cases of pityriasis lichenoides were also studied. The t(2;5) translocation was not present in any of these specimens. To determine if some other somatic mutation might have resulted in inappropriate expression of ALK catalytic domain, we devised an RNA-based reverse transcriptase-PCR assay to detect transcripts encoded by this ALK region. None were found in the six additional cases of lymphomatoid papulosis that were studied. In aggregate, these results strongly suggest that inappropriate expression of ALK is not involved in the pathogenesis of these CD30+ lymphoproliferative disorders, and that lymph node-based CD30+ large cell lymphoma is a disease that is biologically distinct from skin-based CD30+ lymphoproliferative disorders and Hodgkin's disease. Using methods developed for this report, we also cloned and sequenced the t(2;5) genomic junctional sequences present in the SUP-M2 and SU-DHL-1 cell lines. These intron sequences will be useful for mapping t(2;5) breakpoint clusters.
Wood
G S
GS
Department of Dermatology, Case Western Reserve University, Cleveland, OH, USA.
Hardman
D L
DL
Boni
R
R
Dummer
R
R
Kim
Y H
YH
Smoller
B R
BR
Takeshita
M
M
Kikuchi
M
M
Burg
G
G
D000328:Adult; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D001483:Base Sequence; D001665:Binding Sites; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics / Q000648:ultrastructure*; D002895:Chromosomes, Human, Pair 5 / Q000648:ultrastructure*; D004790:Enzyme Induction; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D017730:Ki-1 Antigen / Q000032:analysis; D016403:Lymphoma, Large B-Cell, Diffuse / Q000201:enzymology / Q000235:genetics; D016399:Lymphoma, T-Cell / Q000201:enzymology / Q000235:genetics; D017731:Lymphomatoid Papulosis / Q000201:enzymology / Q000235:genetics; D008232:Lymphoproliferative Disorders / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D017514:Pityriasis Lichenoides / Q000201:enzymology / Q000235:genetics; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases; D016415:Sequence Alignment; D012871:Skin Diseases / Q000201:enzymology / Q000235:genetics*; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D017730:Ki-1 Antigen; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases