Exome sequencing of the TCL1 mouse model for CLL reveals genetic heterogeneity and dynamics during disease development
| Autor: | Roland Geisberger, Nadja Zaborsky, Richard Greil, Daniel Hebenstreit, Maria Schubert, Franz Josef Gassner, Alexander Egle, Daniela Asslaber, Richard Stark, Jan Philip Höpner, Markus Steiner |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research T cell Chronic lymphocytic leukemia B-cell receptor Mice Transgenic Disease Biology Somatic evolution in cancer Article Clonal Evolution RC0254 Genetic Heterogeneity Mice 03 medical and health sciences 0302 clinical medicine immune system diseases Proto-Oncogene Proteins hemic and lymphatic diseases Exome Sequencing medicine Animals Humans Exome Cancer genetics Exome sequencing Genetic heterogeneity Hematology medicine.disease Leukemia Lymphocytic Chronic B-Cell 3. Good health Disease Models Animal 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Mutation Disease Progression Cancer research Disease characteristics |
| Zdroj: | Leukemia |
| ISSN: | 0887-6924 |
| Popis: | The TCL1 mouse model is widely used to study pathophysiology, clonal evolution, and drug sensitivity or resistance of chronic lymphocytic leukemia (CLL). By performing whole exome sequencing, we present the genetic landscape of primary tumors from TCL1 mice and of TCL1 tumors serially transplanted into wild-type recipients to mimic clonal evolution. We show that similar to CLL patients, mutations in mice are frequently subclonal and heterogenous among different primary TCL1 mice. We further describe that this molecular heterogeneity mirrors heterogenous disease characteristics such as organ infiltration or CLL dependent T cell skewing. Similar to human CLL, we further observed the occurrence of novel mutations and structural variations during clonal evolution and found plasticity in the expansion of B cell receptor specific subclones. Thus, our results uncover that the genetic complexity, pathway dependence and clonal dynamics in mouse CLL are in relevant agreement to human CLL, and they are important to consider in future research using the TCL1 mouse for studying CLL. |
| Databáze: | OpenAIRE |
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