Targeted deep sequencing of mycosis fungoides reveals intracellular signaling pathways associated with aggressiveness and large cell transformation
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-250094
- Introduction: Large-cell transformation (LCT) of mycosis fungoides (MF) has been associated with a higher risk of relapse and progression and, consequently, restricted prognosis. Its molecular pathogenesis has not been elucidated yet. Materials and Methods: In order to address molecular mechanisms of LCT, we performed hybrid capture panel-based sequencing of skin biopsies from 10 patients suffering from MF with LCT versus 17 patients without LCT including follow-up biopsies during clinical course, respectively (51 samples in total). TheIntroduction: Large-cell transformation (LCT) of mycosis fungoides (MF) has been associated with a higher risk of relapse and progression and, consequently, restricted prognosis. Its molecular pathogenesis has not been elucidated yet. Materials and Methods: In order to address molecular mechanisms of LCT, we performed hybrid capture panel-based sequencing of skin biopsies from 10 patients suffering from MF with LCT versus 17 patients without LCT including follow-up biopsies during clinical course, respectively (51 samples in total). The analyzed patients were attributed to three different groups based on the presence of LCT and clinical behavior. Results: While indolent MF cases without LCT did not show pathogenic driver mutations, a high rate of oncogenic alterations was detected in patients with LCT and aggressive clinical courses. Various genes of different oncogenic signaling pathways, including the MAPK and JAK-STAT signaling pathways, as well as epigenetic modifiers were affected. A high inter-individual and distinctive intra-individual mutation diversity was observed. Oncogenic RAS mutations were exclusively detected in patients with LCT. Conclusion: Our data demonstrate that LCT transition of MF is associated with increased frequency of somatic mutations in cancer-associated genes. In particular, the activation of RAS signaling — together with epigenetic dysregulation — may crucially contribute to the molecular pathogenesis of the LCT phenotype, thus conveying its adverse clinical behavior.…
Autor(en): | Marion Wobser, Sabine Roth, Silke Appenzeller, Roland Houben, David Schrama, Matthias Goebeler, Eva Geissinger, Andreas Rosenwald, Katja Maurus |
---|---|
URN: | urn:nbn:de:bvb:20-opus-250094 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Pathologisches Institut |
Medizinische Fakultät / Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie | |
Medizinische Fakultät / Comprehensive Cancer Center Mainfranken | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Cancers |
ISSN: | 2072-6694 |
Erscheinungsjahr: | 2021 |
Band / Jahrgang: | 13 |
Heft / Ausgabe: | 21 |
Aufsatznummer: | 5512 |
Originalveröffentlichung / Quelle: | Cancers (2021) 13:21, 5512. https://doi.org/10.3390/cancers13215512 |
DOI: | https://doi.org/10.3390/cancers13215512 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | CD30; cutaneous T-cell-lymphoma; large cell transformation; mycosis fungoides; panel sequencing |
Datum der Freischaltung: | 26.05.2023 |
Datum der Erstveröffentlichung: | 02.11.2021 |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |