Reconstructing clonal evolution in relapsed and non-relapsed Burkitt lymphoma

Reutter, Katrin; Sandmann, Sarah; Rohde, Jonas; Müller, Stephanie; Wöste, Marius; Khanam, Tasneem; Michgehl, Ulf; Klapper, Wolfram; Wößmann, Wilhelm; Seggewiß, Jochen; Lenz, Georg; Dugas, Martin; Burkhardt, Birgit

doi:10.1038/s41375-020-0862-5

Cited by 17 publications

(31 citation statements)

References 14 publications

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“…For all patients, clonal evolution based on WES, targeted sequencing, Sanger sequencing, SNP array analysis (Infinium OmniExpressExome-8v1.3kit) and FISH has been reconstructed manually. Results on clonal evolution, as well as detailed variant calling information (including coverage and variant allele frequency -VAF), have been published (3), original FASTQ files of the WES experiments are available at the Sequence Read Archive (PRJNA561490).…”

Section: Methodsmentioning

confidence: 99%

“…Additionally, the tree plot allows for quick identification of the underlying evolutionary model. Despite this disadvantage of timescape, it is possible to manually improve visualization using additional auxiliary time points, previously described by Reutter et al (3). These time points can be set to force fishplot towards visualization of equidistant development.…”

Section: Datamentioning

confidence: 99%

“…Over the last years, the detection of variants has been greatly optimized (10)(11)(12). However, for the combined evaluation of mutations and their development over time in terms of clonal evolution, many studies still rely on manual analyses (3,13).…”

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confidence: 99%

“…Analyzing two sets of well-characterized, publicaly available real data, we performed a systematic evaluation of currently available tools for automatic reconstruction of clonal evolution, considering all three categories. Data set 1 covers 10 BL patients -5 with and 5 without relapse (3). Data set 2 covers 11 MDS patients -6 patients receiving supportive care and 5 patients treated with lenalidomide (13).…”

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confidence: 99%

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Exploring Current Challenges and Perspectives for Automatic Reconstruction of Clonal Evolution

Sandmann

Richter

Jiang

et al. 2022

Cancer Genomics Proteomics

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Background/Aim: In the field of cancer research, reconstructing clonal evolution is of major interest. The technique provides new insights for analysis and prediction of tumor development. However, reconstruction based on mutational data is characterized by several challenges. Materials and Methods: By performing extensive literature research, we identified 51 currently available tools for reconstructing clonal evolution. By analyzing two cancer data sets (n=21), we investigated the applicability and performance of each tool. Results: Seventeen out of 51 tools could be applied to our data. Correct clustering of variants can be observed for 4 patients in the presence of ≤3 clusters and ≥5 time points. Correct phylogenetic trees are determined for 10 patients. Accurate visualization is possible, by applying adjustments to the original algorithms. Conclusion: Despite bearing considerable potential, automatic reconstruction of clonal evolution remains challenging. To replace tedious manual reconstruction, further research including systematic error analyses using simulation tools needs to be conducted.According to the International Agency for Research on Cancer, more than 19 million new cases of cancer were registered in 2020. Furthermore, almost 10 million deaths were recorded (1). For many types of cancer, precise mutational characterization is of major interest: For Burkitt lymphoma (BL), for example, translocations affecting the MYC gene are considered a biological hallmark and essential in terms of diagnosis (2). Furthermore, recent data shows that relapse may be associated with a deficiency of TP53 (3). 194This article is freely accessible online.

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Section: Methodsmentioning

confidence: 99%

Section: Datamentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Exploring Current Challenges and Perspectives for Automatic Reconstruction of Clonal Evolution

Sandmann

Richter

Jiang

et al. 2022

Cancer Genomics Proteomics

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“…However, new approaches with CAR T-cell products, bispecific antibodies, or antibody–drug conjugates adequately adapted to NHL disease kinetics may pave the way for increasing remission rates before HSCT and higher survival rates in consequence. In parallel, increasing knowledge on NHL biology and molecular genetic characterization has already contributed to identifying genetically defined subgroups [ 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. The era of targeted therapy, small molecules and gene editing will provide new perspectives for patients with refractory or relapsed NHL.…”

Section: Discussionmentioning

confidence: 99%

Treatment and Outcome Analysis of 639 Relapsed Non-Hodgkin Lymphomas in Children and Adolescents and Resulting Treatment Recommendations

Burkhardt

Taj

Garnier

et al. 2021

Cancers

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Despite poor survival, controversies remain in the treatment for refractory or relapsed pediatric non-Hodgkin lymphoma (r/r NHL). The current project aimed to collect international experience on the re-induction treatment of r/r NHL, hematopoietic stem cell transplantation (HSCT), risk factors associated with outcome, and to suggest treatment recommendations. Inclusion criteria were (i) refractory disease, disease progression or relapse of any NHL subtype except anaplastic large cell lymphoma, (ii) age < 18 years at initial diagnosis, (iii) diagnosis in/after January 2000. Data from 639 eligible patients were evaluable. The eight-year probability of overall survival was 34 ± 2% with highly significant differences according to NHL subtypes: 28 ± 3% for 254 Burkitt lymphoma/leukemia, 50 ± 6% for 98 diffuse large B-cell lymphomas, 57 ± 8% for 41 primary mediastinal large B-cell lymphomas, 27 ± 3% for 177 T-lymphoblastic lymphomas, 52 ± 10% for 34 precursor-B-cell lymphoblastic lymphomas and 30 ± 9% for 35 patients with rare NHL subtypes. Subtype-specific factors associated with survival and treatment recommendations are suggested. There were no survivors without HSCT, except in few very small subgroups. Conclusions: There is an urgent need to further improve survival in r/r NHL. The current study provides the largest real-world series, which underlines the role of HSCT and suggests treatment recommendations.

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Epstein–Barr virus and malaria upregulate AID and APOBEC3 enzymes, but only AID seems to play a major mutagenic role in Burkitt lymphoma

et al. 2022

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Endemic Burkitt lymphoma (eBL) is characterized by an oncogenic IGH/c-MYC translocation and Epstein-Barr virus (EBV) positivity, and is epidemiologically linked to Plasmodium falciparum malaria. Both EBV and malaria are thought to contribute to eBL by inducing the expression of activation-induced cytidine deaminase (AID), an enzyme involved in the IGH/c-MYC translocation. AID/apolipoprotein B mRNA editing catalytic polypeptidelike (AID/APOBEC) family enzymes have recently emerged as potent mutagenic sources in a variety of cancers, but apart from AID, their involvement in eBL and their regulation by EBV and P. falciparum is unknown. Here, we show that upon inoculation with EBV, human B cells strongly upregulate the expression of enzymatically active APOBEC3B and APOBEC3G. In addition, we found significantly increased levels of APOBEC3A in B cells of malaria patients, which correlated with parasite load. Interestingly, despite the fact that APOBEC3A, APOBEC3B, and APOBEC3G caused c-MYC mutations when overexpressed in HEK293T cells, a mutational enrichment in eBL tumors was only detected in AID motifs. This suggests that even though the EBV-and P. falciparum-directed immune response triggers the expression and activity of several AID/APOBEC members, only the upregulation of AID has oncogenic consequences, while the induction of the APOBEC3 subfamily may primarily have immunoprotective functions.

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Reconstructing clonal evolution in relapsed and non-relapsed Burkitt lymphoma

Cited by 17 publications

References 14 publications

Exploring Current Challenges and Perspectives for Automatic Reconstruction of Clonal Evolution

Exploring Current Challenges and Perspectives for Automatic Reconstruction of Clonal Evolution

Treatment and Outcome Analysis of 639 Relapsed Non-Hodgkin Lymphomas in Children and Adolescents and Resulting Treatment Recommendations

Epstein–Barr virus and malaria upregulate AID and APOBEC3 enzymes, but only AID seems to play a major mutagenic role in Burkitt lymphoma

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