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The mutational landscape of ocular marginal zone lymphoma identifies frequent alterations in TNFAIP3 followed by mutations in TBL1XR1 and CREBBP.

ABSTRACT: Ocular marginal zone lymphoma is a common type of low-grade B-cell lymphoma. To investigate the genomic changes that occur in ocular marginal zone lymphoma, we analyzed 10 cases of ocular marginal zone lymphoma using whole-genome and RNA sequencing and an additional 38 cases using targeted sequencing. Major genetic alterations affecting genes involved in nuclear factor (NF)-?B pathway activation (60%), chromatin modification and transcriptional regulation (44%), and B-cell differentiation (23%) were identified. In whole-genome sequencing, the 6q23.3 region containing TNFAIP3 was deleted in 5 samples (50%). In addition, 5 structural variation breakpoints in the first intron of IL20RA located in the 6q23.3 region was found in 3 samples (30%). In targeted sequencing, a disruptive mutation of TNFAIP3 was the most common alteration (54%), followed by mutations of TBL1XR1 (18%), cAMP response element binding proteins (CREBBP) (17%) and KMT2D (6%). All TBL1XR1 mutations were located within the WD40 domain, and TBL1XR1 mutants transfected into 293T cells increased TBL1XR1 binding with nuclear receptor corepressor (NCoR), leading to increased degradation of NCoR and the activation of NF-?B and JUN target genes. This study confirms genes involving in the activation of the NF-kB signaling pathway is the major driver in the oncogenesis of ocular MZL.

SUBMITTER: Jung H

PROVIDER: S-EPMC5370020 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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The mutational landscape of ocular marginal zone lymphoma identifies frequent alterations in TNFAIP3 followed by mutations in TBL1XR1 and CREBBP.

Jung Hyunchul H Yoo Hae Yong HY Lee Seung Ho SH Shin Sohyun S Kim Sang Cheol SC Lee Sejoon S Joung Je-Gun JG Nam Jae-Yong JY Ryu Daeun D Yun Jae Won JW Choi Jung Kyoon JK Ghosh Ambarnil A Kim Kyeong Kyu KK Kim Seok Jin SJ Kim Won Seog WS Park Woong-Yang WY Ko Young Hyeh YH

Oncotarget 20170301 10

Ocular marginal zone lymphoma is a common type of low-grade B-cell lymphoma. To investigate the genomic changes that occur in ocular marginal zone lymphoma, we analyzed 10 cases of ocular marginal zone lymphoma using whole-genome and RNA sequencing and an additional 38 cases using targeted sequencing. Major genetic alterations affecting genes involved in nuclear factor (NF)-κB pathway activation (60%), chromatin modification and transcriptional regulation (44%), and B-cell differentiation (23%) ...[more]

PMID: 28152507

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Project description:Background and Objectives: Extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT) type is the most common subtype of the ocular adnexal lymphoma. Despite its excellent prognosis, some patients experience partial remission or progressive disease. We aimed to evaluate clinicopathologic differences in the treatment responder group by comparing complete remission (CR) and non-complete remission (non-CR). Materials and Methods: This study retrospectively reviewed 48 patients who were diagnosed with ocular adnexal MALT lymphoma at Ulsan University Hospital between March 2002 and August 2018. Patients who were followed up for less than 6 months were excluded. Histologic and clinical features were analyzed. The patients were divided into two groups: CR and non-CR. Results: Among the 48 patients, 33 achieved CR and 15 achieved non-CR during the median follow-up period of 40.00 months (range, 7-109 months). In univariable analysis, more patients tend to undergo treatment in the CR group, and post-radiotherapy (post-RT) SUVmax, PET and serum lactate dehydrogenase (LDH) levels were higher in the non-CR group (p = 0.043, p = 0.016, and p = 0.042, respectively). In a multivariable analysis, only application of treatment, including radiotherapy or chemotherapy with immunotherapy, was related to CR (odd ratio 7.301, 95% confidence interval 1.273-41.862, p = 0.026). In subgroup analysis according to the site of involvement, none of the variables were significant except for the post-RT SUVmax of PET and level of serum LDH in the non-conjunctiva group (p = 0.026, and p = 0.037, respectively). Seven (14.6%) patients had a recurrence, and those with a recurring site other than the primary site had a higher Ki-67 labeling index, although it was not statistically significant (9.56% vs. 18.00%, p = 0.095). Conclusions: Although belonging to the early stages, the non-CR rate was high in patients with high serum LDH levels, and recurred patients had higher Ki-67. Thus, considering active treatment is recommended in this group of patients.

Dataset Information

The mutational landscape of ocular marginal zone lymphoma identifies frequent alterations in TNFAIP3 followed by mutations in TBL1XR1 and CREBBP.

Publications

The mutational landscape of ocular marginal zone lymphoma identifies frequent alterations in TNFAIP3 followed by mutations in TBL1XR1 and CREBBP.

Similar Datasets

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