Whole exome sequencing hints at a unique mutational profile of paediatric T‐cell lymphoblastic lymphoma

Bonn, Bettina R.; Huge, Andreas; Rohde, Marius; Oschlies, Ilske; Klapper, Wolfram; Voss, Reinhard; Makarova, Olga; Jürgens, Heribert; Seggewiß, Jochen; Burkhardt, Birgit

doi:10.1111/bjh.13105

Cited by 30 publications

(29 citation statements)

References 10 publications

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“…Interestingly, however, only a Burkitt lymphoma case had a BCOR mutation, and it was a missense mutation (S1295T) (Supporting Information Table 18). In T‐cell lymphomas, no BCOR mutations were identified in angioimmunoblastic T‐cell lymphomas (0/6) (Sakata‐Yanagimoto et al, ) or pediatric T‐cell lymphoblastic lymphomas (0/5) (Bonn et al, ). Therefore, in contrast to STAT3 mutations, which were also detected in other types of lymphomas including diffuse large B‐cell lymphomas (∼10%), BCOR aberrations may be characteristic to ENKTL among lymphoid malignancies, although further studies are needed for T‐cell lymphomas.…”

Section: Discussionmentioning

confidence: 99%

Frequent BCOR aberrations in extranodal NK/T‐Cell lymphoma, nasal type

Dobashi

Tsuyama

Asaka

et al. 2016

Genes Chromosomes & Cancer

108

113

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Extranodal natural killer/T cell lymphoma (ENKTL) is a rare subtype of lymphoma. Recurrent mutations in the JAK-STAT pathway, recently reported in ENKTL cases, are interesting in terms of both pathogenesis and inhibitor therapy. However, the frequencies of these mutations are low and variable among reports, and other pathognomonic mutations in ENKTL remain to be elucidated. In the present study, targeted capture sequencing of 602 cancer-related genes from 25 frozen ENKTL samples was performed, 11 of which were matched to normal samples. Several recurrent somatic mutations involving BCOR (32%), TP53 (16%), DDX3X (12%), FAT4 (8%), NRAS (8%), MLL3 (12%), and MIR17HG (8%) were identified. The pattern of BCOR aberrations (1 nonsense and 5 frame-shift mutations, a mutation leading to a splicing error, and gene loss) suggested that loss of function of BCOR was the functionally important outcome of such changes. The literature was reviewed and the public data on BCOR aberrations was reanalyzed and it was found that the aberrations were frequently found in myeloid neoplasms, but, interestingly, were highly specific to ENKTL among lymphoid malignancies. Given the high frequency and pattern of aberration, BCOR is likely to play an important role in ENKTL pathogenesis as a tumor suppressor gene.

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Section: Discussionmentioning

confidence: 99%

Frequent BCOR aberrations in extranodal NK/T‐Cell lymphoma, nasal type

Dobashi

Tsuyama

Asaka

et al. 2016

Genes Chromosomes & Cancer

108

113

View full text Add to dashboard Cite

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“…The same group is also using whole exome sequencing to identify other genes of interest and have recently published preliminary data which hint at differences between T-LBL and T-ALL [37]. Additional cases will need to be studied to determine prognostic significance of other molecular abnormalities and potential therapeutic interventions.…”

Section: Lymphoblastic Lymphomamentioning

confidence: 99%

Non-Hodgkin Lymphoma in Children

Sandlund

2015

Curr Hematol Malig Rep

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The non-Hodgkin lymphomas (NHLs) of childhood include high-grade mature B cell lymphoma [Burkitt lymphoma (BL), diffuse large B cell lymphoma (DLBCL), and primary mediastinal large B cell lymphoma (PMLBCL)], anaplastic large cell lymphoma (ALCL), and lymphoblastic lymphoma (LL). The prognosis for children with NHL is generally excellent, although there are some higher risk groups. In this regard, PMLBCL is generally associated with a poorer outcome than BL or DLBCL of comparable stage. The long-term event-free survival for children with ALCL is approximately 70 %. Novel biological agents, including those that target CD-30 or ALK, may hold promise for improving treatment results. Children with LL are treated with regimens derived from those used to treat acute lymphoblastic leukemia (ALL). Recent biological study of LL may provide insights into revising treatment stratification. The challenge in pediatric NHL, a group that already has a relatively good prognosis, is to improve treatment outcome without increasing concerning late effects.

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“…Recently, the first whole exome sequence analysis of five paediatric T‐LBL cases was reported (Bonn et al , ). When compared to prior T‐ALL studies (Zhang et al , ; De Keersmaecker et al , ; Neumann et al , ; Tzoneva et al , ), over 40 mutated genes were found exclusively in T‐LBL (Bonn et al , ), alluding to potential genetic differences between these related cancers. Going forward, larger T‐LBL series are needed to verify and potentially expand this list of genetic discriminators.…”

Section: T Lymphoblastic Lymphomamentioning

confidence: 99%

Molecular genetics of childhood, adolescent and young adult non‐Hodgkin lymphoma

2016

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Summary Molecular genetic abnormalities are ubiquitous in non-Hodgkin lymphoma (NHL), but genetic changes are not yet used to define specific lymphoma subtypes. Certain recurrent molecular genetic abnormalities in NHL underlie molecular pathogenesis and/or are associated with prognosis or represent potential therapeutic targets. Most molecular genetic studies of B- and T-NHL have been performed on adult patient samples, and the relevance of many of these findings for childhood, adolescent and young adult NHL remains to be demonstrated. In this review, we focus on NHL subtypes that are most common in young patients and emphasize features actually studied in younger NHL patients. This approach highlights what is known about NHL genetics in young patients but also points to gaps that remain, which will require cooperative efforts to collect and share biological specimens for genomic and genetic analyses in order to help predict outcomes and guide therapy in the future.

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Whole exome sequencing hints at a unique mutational profile of paediatric T‐cell lymphoblastic lymphoma

Cited by 30 publications

References 10 publications

Frequent BCOR aberrations in extranodal NK/T‐Cell lymphoma, nasal type

Frequent BCOR aberrations in extranodal NK/T‐Cell lymphoma, nasal type

Non-Hodgkin Lymphoma in Children

Molecular genetics of childhood, adolescent and young adult non‐Hodgkin lymphoma

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