Tumor suppressor TNFAIP3 (A20) is frequently deleted in Sézary syndrome

Braun, Floriane; Grabarczyk, Piotr; Möbs, Markus; Braun, Frank; Eberle, Jürgen; Beyer, Marc; Sterry, Wolfram; Busse, Frank; Schröder, J; Delin, Martin; Przybylski, Grzegorz K.; Schmidt, Christian A.

doi:10.1038/leu.2011.101

Cited by 54 publications

(59 citation statements)

References 27 publications

(34 reference statements)

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“…Deletion of the CDKN2A gene at the 9p21 locus (Laharanne et al, 2010;Vermeer et al, 2008) has been confirmed in approximately half of SS patients as reported in other NGS studies, which also have shown that the presence of CDKN2A inactivating mutations in a subset of patients (Choi et al, 2015;Kiel et al, 2015;Wang et al, 2015). Genetic loss at 6q23e27 of TNFAIP3, initially detected in half of SS samples, has been confirmed only in a single NGS study (Braun et al, 2011;Choi et al, 2015). Finally, except when single nucleotide polymorphism array analysis was associated (Wang et al, 2015), most NGS studies, including the one by Prasad et al (2016), have not reported gain of MYC and/or loss of its antagonist MNT, which have been recovered in 76% of patients with SS (Boonk et al, 2016;Vermeer et al, 2008).…”

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confidence: 76%

Sézary Syndrome: Translating Genetic Diversity into Personalized Medicine

Chevret

Merlio

2016

Journal of Investigative Dermatology

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Sézary syndrome is probably the most studied cutaneous T-cell lymphoma subtype. Beyond the consensus criteria for Sézary syndrome diagnosis, Sézary cells display heterogeneous phenotypes and differentiation profiles. In the face of SS diversity, the great hope is to develop targeted therapies based on next-generation sequencing to define the genetic landscape of Sézary syndrome. Prasad et al. report on the use of exome sequencing and RNA sequencing to study selected CD4(+) blood cells from 15 patients with erythroderma Sézary syndrome, 14 of whom fulfilled the conventional criteria for diagnosis. The most common genetic abnormality, TP53 gene deletion on chromosome arm 17p and/or mutation, was observed in 58% of patients. However, mutations affecting PLCG1, STAT5B, GLI3, and CARD11 each were detected in only one individual. Nevertheless, Prasad et al. report single point mutations or copy number alterations in several new genes and in new fusion genes, with predicted biological relevance. This information underscores the diversity of genetic alterations and of the mechanisms of alterations of single genes. At the individual level, Sézary cells may combine alterations of genes involved in T-cell signaling, NF-kB and JAK-signal transducer and activator of transcription pathways, apoptosis control, chromatin remodeling, and DNA damage response. The therapeutic relevance of these potential targets needs to be evaluated with tests of function.

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confidence: 76%

Sézary Syndrome: Translating Genetic Diversity into Personalized Medicine

Chevret

Merlio

2016

Journal of Investigative Dermatology

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“…A20, a zinc-finger protein, has been found to have an effect on the pathogenesis of multiple cancers, suggesting an oncogenic role. However, deletions, mutations and inactivations of A20 have been identified in several different subtypes of lymphomas, including Hodgkin lymphomas, primary mediastinal B cell lymphomas [21,22], non-Hodgkin lymphomas [23] and Sézary syndrome [24]. These data suggest that A20 may also act as a tumor suppressor in some types of lymphomas.…”

Section: Discussionmentioning

confidence: 96%

Up-regulated A20 promotes proliferation, regulates cell cycle progression and induces chemotherapy resistance of acute lymphoblastic leukemia cells

Chen

Xing

et al. 2015

Leukemia Research

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“…Recently, bi- and monoallelic A20 deletions in a high proportion of Sezary syndrome patients and a biallelic A20 deletion in the Sezary syndrome-derived cell line SeAx were identified. Furthermore, A20 inhibition activates the NF-κB pathway, thereby increasing the proliferation of normal T-cells [17]. Interestingly, we recently found that there are rare A20 mutations and polymorphisms in T-ALL [25].…”

Section: Introductionmentioning

confidence: 99%

Characteristics of CARMA1-BCL10-MALT1-A20-NF-κB expression in T cell-acute lymphocytic leukemia

Liao

et al. 2014

Eur J Med Res

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BackgroundKnowledge of the oncogenic signaling pathways of T-cell acute lymphoblastic leukemia (T-ALL) remains limited. Constitutive aberrant activation of the nuclear factor kappa B (NF-κB) signaling pathway has been detected in various lymphoid malignancies and plays a key role in the development of these carcinomas. The zinc finger-containing protein, A20, is a central regulator of multiple NF-κB-activating signaling cascades. A20 is frequently inactivated by deletions and/or mutations in several B-and T-cell lymphoma subtypes. However, few A20 mutations and polymorphisms have been reported in T-ALL. Thus, it is of interest to analyze the expression characteristics of A20 and its regulating factors, including upstream regulators and the CBM complex, which includes CARMA1, BCL10, and MALT1.MethodsThe expression levels of CARMA1, BCL10, MALT1, A20, and NF-κB were detected in peripheral blood mononuclear cells (PBMCs) from 21 patients with newly diagnosed T-ALL using real-time PCR, and correlations between the aberrant expression of these genes in T-ALL was analyzed. Sixteen healthy individuals, including 10 males and 6 females, served as controls.ResultsSignificantly lower A20 expression was found in T-ALL patients (median: 4.853) compared with healthy individuals (median: 8.748; P = 0.017), and significantly increased expression levels of CARMA1 (median: 2.916; P = 0.034), BCL10 (median: 0.285; P = 0.033), and MALT1 (median: 1.201; P = 0.010) were found in T-ALL compared with the healthy individuals (median: 1.379, 0.169, and 0.677, respectively). In contrast, overexpression of NF-κB (median: 0.714) was found in T-ALL compared with healthy individuals (median: 0.335; P = 0.001). A negative correlation between the MALT1 and A20 expression levels and a positive correlation between CARMA1 and BCL10 were found in T-ALL and healthy individuals. However, no negative correlation was found between A20 and NF-κB and the MALT1 and NF-κB expression level in the T-ALL group.ConclusionsWe characterized the expression of the CARMA-BCL10-MALT1-A20-NF-κB pathway genes in T-ALL. Overexpression of CARMA-BCL10-MALT in T-ALL may contribute to the constitutive cleavage and inactivation of A20, which enhances NF-κB signaling and may be related to T-ALL pathogenesis.

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Tumor suppressor TNFAIP3 (A20) is frequently deleted in Sézary syndrome

Cited by 54 publications

References 27 publications

Sézary Syndrome: Translating Genetic Diversity into Personalized Medicine

Sézary Syndrome: Translating Genetic Diversity into Personalized Medicine

Up-regulated A20 promotes proliferation, regulates cell cycle progression and induces chemotherapy resistance of acute lymphoblastic leukemia cells

Characteristics of CARMA1-BCL10-MALT1-A20-NF-κB expression in T cell-acute lymphocytic leukemia

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