CD30-positive lymphoproliferations and mycosis fungoides originate from the same T-cell clone and share overlapping oncogenic mutations and gene fusions when occurring in the same patient. (October 2021)

• Record Type: Journal Article
• Authors: Wobser, Marion; Roth, Sabine; Appenzeller, Silke; Kneitz, Hermann; Goebeler, Matthias; Geissinger, Eva; Rosenwald, Andreas; Maurus, Katja
• Is Part Of: European journal of cancer. Volume 156(2021)Supplement 1
• Page Start: S43
• Publication Date: 2021-10
• Subjects: CD30-positive lymphoproliferation -- cutaneous lymphoma -- lymphomatoid papulosis -- mycosis fungoides -- genetic screening; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/S0959-8049(21)00706-1
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract : 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.