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Abstract
Deciphering the evolution of cancer cells under therapeutic pressure is a crucial step to understand the mechanisms that lead to treatment resistance. To this end, we analyzed whole-exome sequencing data of eight chronic lymphocytic leukemia (CLL) patients that developed resistance upon BCL2-inhibition by venetoclax. Here, we report recurrent mutations in BTG1 (2 patients) and homozygous deletions affecting CDKN2A/B (3 patients) that developed during treatment, as well as a mutation in BRAF and a high-level focal amplification of CD274 (PD-L1) that might pinpoint molecular aberrations offering structures for further therapeutic interventions.
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1 Department of Internal Medicine I, Center of Integrated Oncology Cologne-Bonn, University of Cologne, 50937 Cologne, Germany
2 Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany
3 Department of Internal Medicine I, Center of Integrated Oncology Cologne-Bonn, University of Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Response in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany
4 Department of Internal Medicine I, Center of Integrated Oncology Cologne-Bonn, University of Cologne, 50937 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Response in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany
5 Department of Internal Medicine I, Center of Integrated Oncology Cologne-Bonn, University of Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Response in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany; Laboratory of Lymphocyte Signaling and Oncoproteom, University of Cologne, 50931 Cologne, Germany
6 Department of Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases and Tropical Medicine, Klinikum Schwabing, 80804 Munich, Germany
7 Department of Radiology, Cologne University Hospital, 50937 Cologne, Germany
8 Department of Diagnostic and Interventional Radiology and Pediatric Radiology, Städtisches Klinikum München Schwabing, 80804 Munich, Germany
9 Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany; Cologne Center for Genomics (CCG), University of Cologne, 50931 Cologne, Germany
10 Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Response in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany; Cologne Center for Genomics (CCG), University of Cologne, 50931 Cologne, Germany
11 Computing Center, University of Cologne, 50931 Cologne, Germany
12 Computing Center, University of Cologne, 50931 Cologne, Germany; Department of Informatics, University of Cologne, 50931 Cologne, Germany
13 Department of Pathology, University of Cologne, Cologne, Germany