LYMPHOMATOID PAPULOSIS AND ASSOCIATED CUTANEOUS LYMPHOPROLIFERATIVE DISORDERS EXHIBIT A COMMON CLONAL ORIGIN

Determination of the clonal relationship among multiple lymphoprolifer ative disorders occurring in individual patients has been hampered by dependence on molecular biologic techniques that require analysis of a dvanced lesions containing high tumor clone densities to isolate domin ant, clonal antigen-receptor gene rearrangements. Polymerase chain rea ction/denaturing gradient gel electrophoresis (PCR/DGGE) involves the amplification of T-cell receptor (TCR)-gamma gene rearrangements follo wed by their electrophoresis in denaturing gradient gels. This method detects dominant TCR-gamma gene rearrangements at tumor clone densitie s as low as 0.1%, making this assay suitable for analysis of early as well as late lesions, Using this approach, we analyzed skin lesions of lymphomatoid papulosis and either CD30(+) large-cell lymphoma or earl y patch/plaque mycosis fungoides that developed in three patients. In each case, the dual specimens exhibited an identical band pattern by P CR/DGGE analysis, suggesting a common clonal origin. To confirm this c lonal relationship, the dominant TCR-gamma gene rearrangements were el uted, amplified, cloned, and sequenced. In each case, they showed iden tical junctional sequences. These findings are significant for several reasons: 1) they demonstrate the common clonal origin of lymphomatoid papulosis and CD30(+) large-cell lymphoma or mycosis fungoides occurr ing in individual patients; 2) they confirm that co-migrating PCR/DGGE bands exhibit identical nucleotide sequences; and 3) they provide a m ethod for determining the sequence of a tumor-derived TCR-gamma gene r earrangement in early lesions containing a low tumor clone density. Th is latter feature should allow the prospective molecular staging of ea rly cutaneous lymphoproliferative disorders.