Introduction

The emergence of a common progenitor cell has been postulated for the association of CD30-positive lymphoproliferative disease (LPD) and mycosis fungoides (MF) within the same patient. The underlying molecular alterations are unknown.

Materials and methods

We analyzed the underlying genetic alterations of 16 samples of two patients suffering both from CD30-positive LPD and MF. Skin biopsies of respective lesions were obtained over a time course of at least 5 years. We applied targeted next generation sequencing technologies with a hybrid capture-based DNA library preparation approach to detect mutations. For the identification of fusion transcripts we took advantage of an anchored multiplex PCR next generation sequencing assay.

Results

Oncogenic fusions affecting the JAK/STAT signaling pathway were present in all samples obtained both of lesions of CD30-positive LPD and MF. We identified a NPM1-TYK2 fusion in patient 1 and an ILF3-JAK2 fusion in patient 2. In one patient, only the lesions of histologically proven CD30-positive LPD exhibited additional STAT5A mutations that were not present in the MF lesions.

Conclusion

CD30-positive LPD and MF show overlapping molecular profiles when occurring within the same patients. Our data imply that constitutive activation of the JAK/STAT signaling pathway by means of mutations and fusions may play a central role for the molecular pathogenesis of both entities.