作者
Emma Kroeze,Ingram Iaccarino,Michelle M Kleisman,Mayukh Mondal,Thomas Beder,Mouhamad Khouja,Marc P. Hoeppner,Marijn A. Vermeulen,Lennart Kester,Monika Brüggemann,Claudia D. Baldus,Gunnar Cario,Reno S. Bladergroen,Nathalie Garnier,Andishe Attarbaschi,Jaime Verdú‐Amorós,Rosemary Sutton,Elizabeth Macintyre,Kirsten Scholten,Laura Padilla,Birgit Burkhardt,Auke Beishuizen,Monique L. den Boer,Roland P. Kuiper,Jan Loeffen,Judith M. Boer,Wolfgang Hiddemann
摘要
Abstract Pediatric B-cell precursor (BCP) lymphoblastic malignancies are neoplasms with manifestation either in bone marrow/blood (BCP acute lymphoblastic leukemia, BCP-ALL) or less common in extramedullary tissue (BCP lymphoblastic lymphoma, BCP-LBL). Although both presentations are similar in morphology and immunophenotype molecular studies are virtually restricted to BCP-ALL so far. The lack of molecular studies on BCP-LBL is probably due to its rarity and the restriction to tiny, mostly formalin-fixed paraffin embedded (FFPE) tissues. Here we present the first comprehensive mutational and transcriptional analysis of what we consider the largest BCP-LBL cohort described to date (n=97). Whole exome sequencing indicates a mutational spectrum of BCP-LBL strikingly similar to that found in BCP-ALL. However, epigenetic modifiers were more frequently mutated in BCP-LBL, whereas BCP-ALL was more frequently affected by mutation in genes involved in B-cell development. Integrating copy number alterations, somatic mutations and gene expression by RNA-sequencing revealed virtually all molecular subtypes originally defined in BCP-ALL to be present in BCP-LBL too, with only 7% of lymphomas that were not assigned to a subtype. Therefore, the results here described may pave the way for molecular risk adapted treatment protocols for BCP-LBL patients. Keypoints Comprehensive molecular characterization of B-cell precursor lymphoblastic lymphoma allows molecular subtyping analogous to leukemias Compared to leukemias, lymphomas show more alterations in epigenetic modifiers and less in B-cell development genes