Histone modifier gene mutations in peripheral T-cell lymphoma not otherwise specified

Ji, Mengmeng; Huang, Yan‐Jiun; Huang, Jinyan; Wang, Zhaofu; Fu, Di; Liu, Han; Liu, Feng; Lebœuf, Christophe; Wang, Li; Ye, Jing; Lu, Yiming; Janin, Anne; Cheng, Shu; Zhao, Wei‐Li

doi:10.3324/haematol.2017.182444

Cited by 78 publications

(81 citation statements)

References 37 publications

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“…The next generation sequencing approach has recently led to the discovery of recurrent somatic mutations of genes involved in the epigenetic regulation (KMT2D, TET2, KDM6A, DNMT3A, CREBBP, KMT2A), signaling pathways (TNFAIP3, APC, CHD8, ZAP70, NF1, TNFRSF14, TRAF3), and tumor suppression (TP53, FOXO1, BCORL1, ATM) [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Whole exome sequencing reveals mutations in FAT1 tumor suppressor gene clinically impacting on peripheral T-cell lymphoma not otherwise specified

et al. 2020

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Peripheral T-cell lymphoma not otherwise specified represents a diagnostic category comprising clinically, histologically, and molecularly heterogeneous neoplasms that are poorly understood. The genetic landscape of peripheral T-cell lymphoma not otherwise specified remains largely undefined, only a few sequencing studies having been conducted so far. In order to improve our understanding of the genetics of this neoplasm, we performed whole exome sequencing along with RNAsequencing in a discovery set of 21 cases. According to whole exome sequencing results and mutations previously reported in other peripheral T-cell lymphomas, 137 genes were sequenced by a targeted deep approach in 71 tumor samples. In addition to epigenetic modifiers implicated in all subtypes of T-cell neoplasm (TET2, DNMT3A, KMT2D, KMT2C, SETD2), recurrent mutations of the FAT1 tumor suppressor gene were for the first time recorded in 39% of cases. Mutations of the tumor suppressor genes LATS1, STK3, ATM, TP53, and TP63 were also observed, although at a lower frequency. Patients with FAT1 mutations showed inferior overall survival compared to those with wild-type FAT1. Although peripheral T-cell lymphoma not otherwise specified remains a broad category also on molecular grounds, the present study highlights that FAT1 mutations occur in a significant proportion of cases, being provided with both pathogenetic and prognostic impact.

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Section: Introductionmentioning

confidence: 99%

Whole exome sequencing reveals mutations in FAT1 tumor suppressor gene clinically impacting on peripheral T-cell lymphoma not otherwise specified

et al. 2020

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“…325,327 Though there are no targeted agents for KMT2D, the histone deacetylase inhibitors (HDACis) romidepsin and chidamide showed the ability to restore H3K4me3 levels in KMT2D mutant cells in vitro. 328 Chidamide combined with decitabine was observed to induce the apoptosis of Jurkat cells bearing KMT2D mutations in vitro and in vivo. 328 Histone acetylation CREBBP/EP300.…”

Section: Idh2mentioning

confidence: 99%

“…328 Chidamide combined with decitabine was observed to induce the apoptosis of Jurkat cells bearing KMT2D mutations in vitro and in vivo. 328 Histone acetylation CREBBP/EP300. The balance between histone acetyltransferases (HATs, including CREBBP and EP300) and HDACs is critical to maintain a normal histone acetylation status in cells.…”

Section: Idh2mentioning

confidence: 99%

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Advances in targeted therapy for malignant lymphoma

Wang

Qin

Huo

et al. 2020

Sig Transduct Target Ther

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The incidence of lymphoma has gradually increased over previous decades, and it ranks among the ten most prevalent cancers worldwide. With the development of targeted therapeutic strategies, though a subset of lymphoma patients has become curable, the treatment of refractory and relapsed diseases remains challenging. Many efforts have been made to explore new targets and to develop corresponding therapies. In addition to novel antibodies targeting surface antigens and small molecular inhibitors targeting oncogenic signaling pathways and tumor suppressors, immune checkpoint inhibitors and chimeric antigen receptor T-cells have been rapidly developed to target the tumor microenvironment. Although these targeted agents have shown great success in treating lymphoma patients, adverse events should be noted. The selection of the most suitable candidates, optimal dosage, and effective combinations warrant further investigation. In this review, we systematically outlined the advances in targeted therapy for malignant lymphoma, providing a clinical rationale for mechanism-based lymphoma treatment in the era of precision medicine.Signal Transduction and Targeted Therapy (2020) 5:15; https://doi.

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“…The contribution of epigenetic dysregulation to the pathogenesis of MTCL is further supported by many lines of genetic data demonstrating several recurring mutations in genes governing a host of epigenetic functions, including DNMT3A, IDH2, TET2, MLL2, KMT2A, KDM6A, CREBBP, and EP300. [13][14][15][16][17][18] Collectively, the data suggest that there may be "epigenetic vulnerabilities" that can be exploited in a rational therapeutic approach. Mutations in several genes involved in DNA methylation, namely, IDH2, TET2, and DNMT3, were reported in separate publications in 2012.…”

Section: Molecular Pathogenesismentioning

confidence: 99%

The rapidly changing landscape in mature T‐cell lymphoma (MTCL) biology and management

Marchi

O’Connor

2019

CA A Cancer J Clinicians

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Historical advances in the care of patients with non-Hodgkin lymphoma (NHL) have been restricted largely to patients with B-cell lymphoma. The peripheral T-cell lymphomas (PTCLs), which are rare and heterogeneous in nature, have yet to experience the same degree of improvement in outcome over the past 20 to 30 years. It is estimated that there are approximately 80,000 and 14,000 cases, respectively, of NHL and Hodgkin lymphoma per year in the United States. As a subgroup of NHL, the PTCLs account for 6% to 10% of all cases of NHL, making them exceedingly rare. In addition, the World Health Organization 2017 classification describes 29 distinct subtypes of PTCL. This intrinsic diversity, coupled with its rarity, has stymied progress in the disease. In addition, most subtypes carry an inferior prognosis compared with their B-cell counterparts, an outcome largely attributed to the fact that most treatment paradigms for patients with PTCL have been derived from B-cell neoplasms, a radically different disease. In fact, the first drug ever approved for patients with PTCL was approved only a decade ago. The plethora of recent drug approvals in PTCL, coupled with a deeper understanding of the molecular pathogenesis of the disease, has stimulated the field to pursue new avenues of research that are now largely predicated on the development of novel, targeted small molecules, which include a host of epigenetic modifiers and biologics. There is an expectation these advances may begin to favorably challenge the chemotherapy paradigms that have been used in the T-cell malignancies.

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Histone modifier gene mutations in peripheral T-cell lymphoma not otherwise specified

Cited by 78 publications

References 37 publications

Whole exome sequencing reveals mutations in FAT1 tumor suppressor gene clinically impacting on peripheral T-cell lymphoma not otherwise specified

Whole exome sequencing reveals mutations in FAT1 tumor suppressor gene clinically impacting on peripheral T-cell lymphoma not otherwise specified

Advances in targeted therapy for malignant lymphoma

The rapidly changing landscape in mature T‐cell lymphoma (MTCL) biology and management

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