Novel insights into the genetics and epigenetics of MALT lymphoma unveiled by next generation sequencing analyses

Cascione, Luciano; Rinaldi, Andrea; Bruscaggin, Alessio; Tarantelli, Chiara; Arribas, Alberto J.; Kwee, Ivo; Pecciarini, Lorenza; Mensah, Afua Adjeiwaa; Spina, Valeria; Chung, Elaine Y.; Bergamo, Lodovico Terzi di; Dirnhofer, Stephan; Tzankov, Alexandar; Miranda, Roberto N.; Young, Kenneth H.; Traverse-Gléhen, Alexandra; Gaïdano, Gianluca; Swerdlow, Steven H.; Gascoyne, Randy D.; Rabadán, Raúl; Ponzoni, Maurilio; Bhagat, Govind; Rossi, Davide; Zucca, Emanuele; Bertoni, Francesco

doi:10.3324/haematol.2018.214957

Cited by 56 publications

(94 citation statements)

References 15 publications

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“…CREBBP, which is also mutated in other types of B cell lymphomas [33], is an epigenetic regulator, belonging to the KAT3 family of histone/protein lysine acetyltransferases. Mutations were also reported in other studies for the epigenetic regulators KMT2D and KMT2C [16,18]. Therefore, epigenetic dysregulation seems to be involved in the pathogenesis of OAML.…”

Section: Discussionmentioning

confidence: 52%

“…Another candidate gene analysis revealed recurrent mutations in TBL1XR1 (transducin beta like 1 X-linked receptor 1; 6% of cases), TNFRSF14, (tumor necrosis factor receptor family member 14; 5%), and TET2 (tet methycytosine dioxygenase 2; 4% of cases), besides a few less frequently mutated genes [17]. A further candidate gene mutation analysis validated several genes identified by the other studies, mainly adding KMT2C to the list of genes recurrently mutated in OAML [18].…”

Section: Introductionmentioning

confidence: 61%

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Identifying Genetic Lesions in Ocular Adnexal Extranodal Marginal Zone Lymphomas of the MALT Subtype by Whole Genome, Whole Exome and Targeted Sequencing

Johansson

Klein-Hitpaß

Budeus

et al. 2020

Cancers

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The pathogenesis of ocular adnexal marginal zone lymphomas of mucosa-associated lymphatic tissue-type (OAML) is not fully understood. We performed whole genome sequencing (WGS) and/or whole exome sequencing (WES) for 13 cases of OAML and sequenced 38 genes selected from this analysis in a large cohort of 82 OAML. Besides confirmation of frequent mutations in the genes transducin beta like 1 X-linked receptor 1 (TBL1XR1) and cAMP response element binding protein (CREBBP), we newly identifed JAK3 as a frequently mutated gene in OAML (11% of cases). In our retrospective cohort, JAK3 mutant cases had a shorter progression-free survival compared with unmutated cases. Other newly identified genes recurrently mutated in 5–10% of cases included members of the collagen family (collagen type XII alpha 1/2 (COL12A1, COL1A2)) and DOCK8. Evaluation of the WGS data of six OAML did not reveal translocations or a current infection of the lymphoma cells by viruses. Evaluation of the WGS data for copy number aberrations confirmed frequent loss of TNFAIP3, and revealed recurrent gains of the NOTCH target HES4, and of members of the CEBP transcription factor family. Overall, we identified several novel genes recurrently affected by point mutations or copy number alterations, but our study also indicated that the landscape of frequently (>10% of cases) mutated protein-coding genes in OAML is now largely known.

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Section: Discussionmentioning

confidence: 52%

Section: Introductionmentioning

confidence: 61%

Identifying Genetic Lesions in Ocular Adnexal Extranodal Marginal Zone Lymphomas of the MALT Subtype by Whole Genome, Whole Exome and Targeted Sequencing

Johansson

Klein-Hitpaß

Budeus

et al. 2020

Cancers

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“…Microarray data were analyzed as previously described [ 24 ]. RNA-Seq data mining was performed as previously described [ 25 ]. For functional annotation [ 25 ], microarray data were processed with regular gene set enrichment analysis while RNA-Seq data were processed with preranked GSEA (Gene Set Enrichment Analysis) on fold change-ranked values, both using the default GSEA setting.…”

Section: Methodsmentioning

confidence: 99%

Role of ETS1 in the Transcriptional Network of Diffuse Large B Cell Lymphoma of the Activated B Cell-Like Type

Priebe

Sartori

Napoli

et al. 2020

Cancers

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Diffuse large B cell lymphoma (DLBCL) is a heterogenous disease that has been distinguished into at least two major molecular entities, the germinal center-like B cell (GCB) DLBCL and activated-like B cell (ABC) DLBCL, based on transcriptome expression profiling. A recurrent ch11q24.3 gain is observed in roughly a fourth of DLBCL cases resulting in the overexpression of two ETS transcription factor family members, ETS1 and FLI1. Here, we knocked down ETS1 expression by siRNA and analyzed expression changes integrating them with ChIP-seq data to identify genes directly regulated by ETS1. ETS1 silencing affected expression of genes involved in B cell signaling activation, B cell differentiation, cell cycle, and immune processes. Integration of RNA-Seq (RNA sequencing) data and ChIP-Seq (chromatin immunoprecipitation sequencing) identified 97 genes as bona fide, positively regulated direct targets of ETS1 in ABC-DLBCL. Among these was the Fc receptor for IgM, FCMR (also known as FAIM3 or Toso), which showed higher expression in ABC- than GCB-DLBCL clinical specimens. These findings show that ETS1 is contributing to the lymphomagenesis in a subset of DLBCL and identifies FCMR as a novel target of ETS1, predominantly expressed in ABC-DLBCL.

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“…Although the analyzed sample size was small, genetic mutations for rare gastrointestinal MALT lymphoma were identified. Various mutations or genetic alterations identified in previous studies using NGS of MALT lymphoma (54,55) were confirmed, and several variations affecting the development of MALT lymphoma for which the exact mechanisms have not yet been elucidated were identified. Hyeon et al (54) analyzed 19 cases of gastric MALT lymphoma using targeted sequencing and the majority of genes affected by genetic alterations were involved in NF-κB pathway activation and included MALT1 rearrangement and somatic mutations of TNF receptor associated factor 3, TNFAIP3 and NOTCH1.…”

Section: Discussionmentioning

confidence: 56%

Mutational analysis of extranodal marginal zone lymphoma using next generation sequencing

Huh

Lee

et al. 2020

Oncol Lett

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Extranodal marginal zone lymphoma is a type of low-grade B-cell lymphoma that can be classified as a mucosal-associated lymphoid tissue (MALT) lymphoma. Recently, second-generation or next-generation sequencing (NGS), which allows simultaneous sequencing of hundreds to billions of DNA strands, has been a focus of attention and is rapidly being adopted in various fields. In the present study, paraffin-embedded tissue samples of gastric MALT lymphoma (n=1) and small intestine MALT lymphoma (n=4) were selected, and DNA was extracted from the tissue samples. After performing quality control, NGS was performed using HemaSCAN™, a custom panel of 426 genes, including essential blood cancer genes. NGS revealed single nucleotide variations (SNVs), short insertions and deletions (InDels) and copy number variations (CNVs). These genomic variants were reported as annotated, known or novel variants. An annotated variant, an erb-b2 receptor tyrosine kinase 2 gene amplification, was observed in one patient. Known and novel variants, including SNVs of SET binding protein 6 (SETBP6), Runt-related transcription factor 1 and Kelch-like ECH-associated protein 1 genes, InDel of the marker of proliferation Ki-67 gene, and CNVs of the zinc finger protein 703 and NOTCH1 genes, were observed in ≥2 patients. Additionally, InDels with frameshift mutations were identified in the B-cell lymphoma/leukemia 10, DEAD-box helicase 3 X-linked, forkhead box O3 and mucin 2, oligomeric mucus/gel-forming genes in one patient. Since few NGS studies have been performed on MALT lymphoma, the current results were unable to determine if the different mutations that were identified are 'actionable' (that is, potentially responsive to a targeted therapy) Further studies are required to determine the associations between genetic mutations and the development of MALT lymphoma.

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Novel insights into the genetics and epigenetics of MALT lymphoma unveiled by next generation sequencing analyses

Cited by 56 publications

References 15 publications

Identifying Genetic Lesions in Ocular Adnexal Extranodal Marginal Zone Lymphomas of the MALT Subtype by Whole Genome, Whole Exome and Targeted Sequencing

Identifying Genetic Lesions in Ocular Adnexal Extranodal Marginal Zone Lymphomas of the MALT Subtype by Whole Genome, Whole Exome and Targeted Sequencing

Role of ETS1 in the Transcriptional Network of Diffuse Large B Cell Lymphoma of the Activated B Cell-Like Type

Mutational analysis of extranodal marginal zone lymphoma using next generation sequencing

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