LACK OF THE T(2-5) OR OTHER MUTATIONS RESULTING IN EXPRESSION OF ANAPLASTIC LYMPHOMA KINASE CATALYTIC DOMAIN IN CD30(-DISEASE() PRIMARY CUTANEOUS LYMPHOPROLIFERATIVE DISORDERS AND HODGKINS)

The t(2;5) (p23;q35) chromosomal translocation has been found in a hig h proportion of lymph node-based CD30(+) large cell lymphomas of T-cel l lineage. This translocation is believed to result in the expression of a fusion protein containing the catalytic domain of anaplastic lymp homa kinase (ALK) under the control of the promoter for nucleophosmin, a nucleolar phosphoprotein. Expression of ALK activity, which does no t normally occur in lymphocytes, is postulated to be involved in the p athogenesis of lymphomas bearing the t(2; 5) translocation. Several pr imary cutaneous lymphoproliferative disorders and Hodgkin's disease ar e also known to contain CD30(+) large lymphoid cells, To determine the role of the t(2;5) translocation in these diseases, we developed a DN A-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 lich enoides were also studied. The t(2;5) translocation was not present in any of these specimens. To determine ii some other somatic mutation m ight have resulted in inappropriate expression of ALK catalytic domain , we devised an RNA-based reverse transcriptase-PCR assay to detect tr anscripts encoded by this ALK region. None were found in the six addit ional cases of lymphomatoid papulosis that were studied. In aggregate, these results strongly suggest that inappropriate expression of ALK i s not involved in the pathogenesis of these CD30(+) lymphoproliferativ e disorders, and that lymph node-based CD30(+) large cell lymphoma is a disease that is biologically distinct from skin-based CD30(+) lympho proliferative disorders and Hodgkin's disease, Using methods developed for this report, we also cloned and sequenced the t(2;5) genomic junc tional sequences present in the SUP-MZ and SU-DHL-1 cell lines. These intron sequences will be useful for mapping t(2;5) breakpoint clusters .