作者
Emma Kroeze,Ingram Iaccarino,Michelle M Kleisman,Mayukh Mondal,Thomas Beder,Mouhamad Khouja,Marc P. Hoeppner,Marijn Scheijde-Vermeulen,Lennart Kester,Monika Brueggemann,Claudia D. Baldus,Gunnar Cario,Reno S. Bladergroen,Nathalie Garnier,Andishe Attarbaschi,Jose Jaime Verdu-Amoros,Rosemary Sutton,Elizabeth Macintyre,Kirsten Scholten,Laura Padilla,Birgit Burkhardt,Auke Beishuizen,Monique L. den Boer,Roland P. Kuiper,Jan Loeffen,Judith M. Boer,Wolfram Klapper
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