Mutational and transcriptional landscape of pediatric B-cell precursor lymphoblastic lymphoma
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 leukemiasCompared to leukemias, lymphomas show more alterations in epigenetic modifiers and less in B-cell development genes.
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 30. Dez. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kroeze, Emma [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2023.12.27.573433 |
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| PPN (Katalog-ID): |
XBI041999134 |
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| 520 | |a 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 leukemiasCompared to leukemias, lymphomas show more alterations in epigenetic modifiers and less in B-cell development genes | ||
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