High-resolution analysis of chromosome copy number alterations in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified, with single nucleotide polymorphism-typing microarrays

Si, Fujiwara; Yamashita, Yuichi; Nakamura, Naoya; Yl, Choi; Ueno, Toshihide; Watanabe, Hideki; Kurashina, Kentaro; Soda, Manabu; Enomoto, Masaya; Hatanaka, Hisashi; Takada, Shuji; M, Abe; Ozawa, Keiya; Mano, Hiroyuki

doi:10.1038/leu.2008.191

Cited by 45 publications

(28 citation statements)

References 36 publications

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“…Overexpression of CARMA1 was reported in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, and it was linked to poor prognosis in a report by Fujiwara et al [35]. Additionally, in a genome profile analysis of aggressive adult T-cell leukemia/lymphoma, CARMA1 was found to be a potential 7p22 amplification target gene in the lymphoma but not acute subtype.…”

Section: Resultsmentioning

confidence: 95%

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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Section: Resultsmentioning

confidence: 95%

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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“…IKZF2 encodes Helios, a T cell-restricted Ikaros-family transcription factor, and is expressed in various PTCLs. [42][43][44][45] IKZF2 was expressed similarly in TCL75 and other cases, whereas ERBB4 was expressed only in TCL75 exons 2 to 28 encoded by IKZF2-ERBB4, which includes the ERBB4 kinase domain (supplemental Figure D-E). Thus, the fusion, which contains only exons 1 to 2 of IKZF2, co-opts the IKZF2 promoter for expression.…”

Section: Mpseq/rnaseq Identifies Novel Kinase Fusions In Ptcl Nosmentioning

confidence: 99%

Integrated mate-pair and RNA sequencing identifies novel, targetable gene fusions in peripheral T-cell lymphoma

Boddicker¹,

Razidlo

Dasari

et al. 2016

Blood

103

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Peripheral T-cell lymphomas (PTCLs) represent a heterogeneous group of T-cell malignancies that generally demonstrate aggressive clinical behavior, often are refractory to standard therapy, and remain significantly understudied. The most common World Health Organization subtype is PTCL, not otherwise specified (NOS), essentially a “wastebasket” category because of inadequate understanding to assign cases to a more specific diagnostic entity. Identification of novel fusion genes has contributed significantly to improving the classification, biologic understanding, and therapeutic targeting of PTCLs. Here, we integrated mate-pair DNA and RNA next-generation sequencing to identify chromosomal rearrangements encoding expressed fusion transcripts in PTCL, NOS. Two of 11 cases had novel fusions involving VAV1, encoding a truncated form of the VAV1 guanine nucleotide exchange factor important in T-cell receptor signaling. Fluorescence in situ hybridization studies identified VAV1 rearrangements in 10 of 148 PTCLs (7%). These were observed exclusively in PTCL, NOS (11%) and anaplastic large cell lymphoma (11%). In vitro, ectopic expression of a VAV1 fusion promoted cell growth and migration in a RAC1-dependent manner. This growth was inhibited by azathioprine, a clinically available RAC1 inhibitor. We also identified novel kinase gene fusions, ITK-FER and IKZF2-ERBB4, as candidate therapeutic targets that show similarities to known recurrent oncogenic ITK-SYK fusions and ERBB4 transcript variants in PTCLs, respectively. Additional novel and potentially clinically relevant fusions also were discovered. Together, these findings identify VAV1 fusions as recurrent and targetable events in PTCLs and highlight the potential for clinical sequencing to guide individualized therapy approaches for this group of aggressive malignancies.

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“…(32) Little is known about its genetics (Table 2). (12)(13)(14)33) In addition to the high frequencies of trisomies of chromosomes 3 and 5, not specific for AITL, (8,11) the most frequent gains have been reported at 11q13, 19, 20q13, and 22q, whereas losses have been reported at 13q22-q32, 8p22, and 9p21 (CDKN2A).…”

Section: Nodal Lymphomasmentioning

confidence: 99%

“…(8)(9)(10)(11)(12)(13)(14)(15)(16) Most frequent gains occur on chromosomal regions 1q32-qter, 2p (2p15-p16), 7q22-ter, 8q (8q24), 9q33-qter, 11q (11q13), and 17q (17cen-q21). Recurrent losses mainly affect 6q (6q21), 9p21, 10 (10cen-p12, 10q23-q24), 13q (13q21), 14q (14q12-q21), 16q (16q11-q21), and 17p (17p13).…”

Section: Nodal Lymphomasmentioning

confidence: 99%

Genetic alterations in systemic nodal and extranodal non‐cutaneous lymphomas derived from mature T cells and natural killer cells

et al. 2012

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Mature (peripheral) T-cell and natural killer (NK)-cell lymphomas comprise a series of rather different neoplasms. Based on morphologic, immunophenotypic, genetic, and clinical data, the World Health Organization classification recognizes more than 20 entities or provisional entities. The variable clinical presentations, the objective recognition and pathological stratification, the difficulties regarding treatment, and the hardly predictable response to therapy indicate that the management of these entities requires novel tools. In contrast to B-cell lymphomas or precursor T-cell neoplasms, few recurrent translocations have been identified so far in T-cell non-Hodgkin's and NK-cell lymphomas. Additionally, some of the entities recognized by the World Health Organization classification are very rare and very scarce molecular data are available for T-cell lymphomas. Here, we have reviewed published reports focusing on the genetic lesions and gene expression profiling underlying systemic nodal and extranodal non-cutaneous mature T-cell and NK-cell lymphomas. We also provide a summary of new agents in clinical development and outline some future directions. (Cancer Sci 2012; 103: 1397-1404

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High-resolution analysis of chromosome copy number alterations in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified, with single nucleotide polymorphism-typing microarrays

Cited by 45 publications

References 36 publications

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

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

Integrated mate-pair and RNA sequencing identifies novel, targetable gene fusions in peripheral T-cell lymphoma

Genetic alterations in systemic nodal and extranodal non‐cutaneous lymphomas derived from mature T cells and natural killer cells

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