Larissa Haertle, Santiago Barrio, Umair Munawar, Seungbin Han, Xiang Zhou, Michal Simicek, Cornelia Vogt, Marietta Truger, Rafael Alonso Fernandez, Maximilian Steinhardt, Julia Weingart, Renata Snaurova, Silvia Nerreter, Eva Teufel, Andoni Garitano-Trojaola, Matteo Da Viá, Yanira Ruiz-Heredia, Andreas Rosenwald, Niccolò Bolli, Roman Hajek, Peter Raab, Marc S Raab, Niels Weinhold, Claudia Haferlach, Thomas Haaf, Joaquin Martinez-Lopez, Hermann Einsele, Leo Rasche, K Martin Kortüm
PURPOSE: Proteasome inhibitors (PI) are the backbone of various treatment regimens in multiple myeloma. We recently described the first in-patient point mutations affecting the 20S subunit PSMB5 underlying PI resistance. Notably, in vivo, the incidence of mutations in PSMB5 and other proteasome encoding genes is too low to explain the development of resistance in most of the affected patients. Thus, additional genetic and epigenetic alterations need to be explored. EXPERIMENTAL DESIGN: We performed DNA methylation profiling by Deep Bisulfite Sequencing in PSMB5, PSMC2, PSMC5, PSMC6, PSMD1, and PSMD5, a subset of proteasome subunits that have hitherto been associated with PI resistance, recruited from our own previous research, the literature, or a meta-analysis on the frequency of somatic mutations...
January 4, 2023: Clinical Cancer Research