Mutational and transcriptional landscape of pediatric B-cell precursor lymphoblastic lymphoma

Kroeze, E.; Iaccarino, I.; Kleisman, M. M.; Mondal, M.; Beder, T.; Khouja, M.; Hoeppner, M. P.; Scheijde-Vermeulen, M.; Kester, L. A.; Brueggemann, M.; Baldus, C. D.; Cario, G.; Bladergroen, R. S.; Garnier, N.; Attarbaschi, A.; Verdu-Amoros, J. J.; Sutton, R.; MacIntyre, E.; Scholten, K.; Padilla, L. A.; Burkhardt, B.; Beishuizen, A.; den Boer, M. L.; Kuiper, R. P.; Loeffen, J. L.; Boer, J. M.; Klapper, W.

doi:10.1101/2023.12.27.573433

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bioRxiv · 10.1101/2023.12.27.573433

Mutational and transcriptional landscape of pediatric B-cell precursor lymphoblastic lymphoma

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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. KeypointsComprehensive 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

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Kroeze, E., Iaccarino, I., Kleisman, M. M., Mondal, M., Beder, T., Khouja, M., Hoeppner, M. P., Scheijde-Vermeulen, M., Kester, L. A., Brueggemann, M., Baldus, C. D., Cario, G., Bladergroen, R. S., Garnier, N., Attarbaschi, A., Verdu-Amoros, J. J., Sutton, R., MacIntyre, E., Scholten, K., Padilla, L. A., Burkhardt, B., Beishuizen, A., den Boer, M. L., Kuiper, R. P., Loeffen, J. L., Boer, J. M., Klapper, W.. 2023-12-27. Mutational and transcriptional landscape of pediatric B-cell precursor lymphoblastic lymphoma. https://doi.org/10.1101/2023.12.27.573433

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