<i>TBL1XR1</i> Mutations in Primary Marginal Zone Lymphomas of Ocular Adnexa are Associated with Unique Morphometric Phenotypes

Jangam, Diwash; Sridhar, Kaushik; Butzmann, Alexandra; Samghabadi, Peyman; Plowey, Edward D.; Ohgami, Robert S.

doi:10.1080/02713683.2020.1762228

Cited by 5 publications

(5 citation statements)

References 27 publications

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“…Venturutti et al (25) found through studies in mice that TBL1XR1 alterations lead to a striking extranodal immunoblastic lymphoma phenotype that mimics the human disease. Jangam et al (26) performed targeted deep sequencing of 8 ocular adnexal mucosa-associated lymphoid tissue lymphoma (OAML) cases, and identified TBL1XR1 as recurrently mutated in OAML (4/8), where cases of OAML with mutations in TBL1XR1 showed equivalent or increased vascular density compared with cases without mutations in TBL1XR1. Wang et al (27) found that patients with primary testicular lymphoma with the TBL1XR1 mutation had an inferior OS than patients with TBL1XR1 wild type, irrespective of treatment therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Jangam et al. ( 26 ) performed targeted deep sequencing of 8 ocular adnexal mucosa-associated lymphoid tissue lymphoma (OAML) cases, and identified TBL1XR1 as recurrently mutated in OAML (4/8), where cases of OAML with mutations in TBL1XR1 showed equivalent or increased vascular density compared with cases without mutations in TBL1XR1 . Wang et al.…”

Section: Discussionmentioning

confidence: 99%

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Circulating Tumor DNA Characteristics Based on Next Generation Sequencing and Its Correlation With Clinical Parameters in Patients With Lymphoma

Hou²,

Zhang³

et al. 2022

Front. Oncol.

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BackgroundLymphoma is a heterogeneous group of tumors in terms of morphological subtypes, molecular alterations, and management. However, data on circulating tumor DNA (ctDNA) mutated genes are limited. The purpose of this study was to investigate the features of the ctDNA mutated genes, the prognosis, and the association between the ctDNA mutated genes and the clinical parameters in lymphoma.MethodsDifferences in the ctDNA between the mutated genes and the prognosis of 59 patients with Hodgkin’s lymphoma (HL) (10.2%), germinal center B-cell–like lymphoma (GCB) (28.8%), nongerminal center B-cell–like lymphoma (non-GCB) (50.8%), and marginal zone lymphoma (MZL) (10.2%) were analyzed by next generation sequencing (NGS) targeting 121 lymphoma-relevant genes.ResultsGenetic alterations were identified in the ctDNA samples with a median of 6 variants per sample. The genetic variation of the ctDNA in the plasma was found to be significantly correlated with the clinical indices in lymphoma. The genetic heterogeneity of different lymphoma subtypes was clearly observed in the ctDNAs from HL, GCB, non-GCB, and MZL, confirming that distinct molecular mechanisms are involved in the pathogenesis of different lymphomas.ConclusionOur findings suggest that NGS-based ctDNA mutation analysis reveals genetic heterogeneity across lymphoma subtypes, with potential implications for discovering therapeutic targets, exploring genomic evolution, and developing risk-adaptive therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Circulating Tumor DNA Characteristics Based on Next Generation Sequencing and Its Correlation With Clinical Parameters in Patients With Lymphoma

Hou²,

Zhang³

et al. 2022

Front. Oncol.

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“…The H&E images were patched at an optical zoom of ×40, uniform width of 68 pixels and height of 57 pixels. MATLAB program (version 2019b; https://www.mathworks.com/ ) was used for image analysis wherein the cells of interest were segmented based on their pixel intensities ( 33 ). The unsharp filter in the Image Processing Toolbox was used to improve the edge contours and contrast among the different cells of interest.…”

Section: Methodsmentioning

confidence: 99%

A comprehensive analysis of RHOA mutation positive and negative angioimmunoblastic T-cell�lymphomas by targeted deep sequencing, expression profiling and single cell digital image analysis

et al. 2020

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Angioimmunoblastic T-cell lymphoma (AITL) is a uniquely aggressive mature T-cell neoplasm. In recent years, recurrent genetic mutations in ras homolog family member A ( RHOA ), tet methylcytosine dioxygenase 2 ( TET2 ), DNA methyltransferase 3 alpha ( DNMT3A ) and isocitrate dehydrogenase [NADP(+)] 2 ( IDH2 ) have been identified as associated with AITL. However, a deep molecular study assessing both DNA mutations and RNA expression profile combined with digital image analysis is lacking. The present study aimed to evaluate the significance of molecular and morphologic features by high resolution digital image analysis in several cases of AITL. To do so, a total of 18 separate tissues from 10 patients with AITL were collected and analyzed. The results identified recurrent mutations in RHOA , TET2 , DNMT3A , and IDH2 , and demonstrated increased DNA mutations in coding, promoter and CCCTC binding factor (CTCF) binding sites in RHOA mutated AITLs vs. RHOA non-mutated cases, as well as increased overall survival in RHOA mutated patients. In addition, single cell computational digital image analysis morphologically characterized RHOA mutated AITL cells as distinct from cells from RHOA mutation negative patients. Computational analysis of single cell morphological parameters revealed that RHOA mutated cells have decreased eccentricity (more circular) compared with RHOA non-mutated AITL cells. In conclusion, the results from the present study expand our understanding of AITL and demonstrate that there are specific cell biological and morphological manifestations of RHOA mutations in cases of AITL.

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“…The H&E images were patched at an optical zoom of x40, uniform width of 68 pixels and height of 57 pixels. MATLAB program (version 2019b; https://www.mathworks.com/) was used for image analysis wherein the cells of interest were segmented based on their pixel intensities (33). The unsharp filter in the Image Processing Toolbox was used to improve the edge contours and contrast among the different cells of interest.…”

Section: Methodsmentioning

confidence: 99%

A Comprehensive Analysis of Rhoa Mutation Positive and Negative Angioimmunoblastic T-Cell Lymphomas By Targeted Deep Sequencing, Expression Profiling, and Single Cell Digital Image Analysis

Butzmann

Sridhar

Jangam

et al. 2019

Blood

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Angioimmunoblastic T-cell lymphoma is a uniquely aggressive mature T-cell neoplasm. In recent years, recurrent genetic mutations in RHOA, TET2, DNMT3A and IDH2 have been identified which characterize this disease. However, a deep molecular study assessing both DNA mutations and RNA expression profile, combined with digital image analysis is lacking. We designed a study to assess the significance of molecular and morphologic features by high resolution digital image analysis in cases of AITL. Eighteen separate tissues from ten patients with AITL were identified and analyzed in this study. Our results confirm recurrent mutations in RHOA, TET2, DNMT3A, and IDH2, and demonstrate increased DNA mutations in coding, promoter and CTCF binding sites in RHOA mutated AITLs versus RHOA non-mutated cases as well as increased overall survival in RHOA mutated patients. In addition, single cell computational digital image analysis morphologically characterized RHOA mutated AITL cells as distinct from cells from RHOA mutation negative patients. Computational analysis of single cell morphological parameters revealed RHOA mutated cells have reduced eccentricity (more circular) compared to RHOA non-mutated AITL cells. Overall, this study expands our understanding of AITL and demonstrates that there are specific cell biologic and morphologic manifestations of RHOA mutations in cases of AITL. KeyPoints: 1) RHOA mutated AITL show distinctly increased and more deleterious mutations than RHOA unmutated cases 2) RHOA mutated T-cells have distinct morphologic features from RHOA unmutated T-cells Disclosures Ohgami: Agilent technologies: Other: received support/funding.

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TBL1XR1 Mutations in Primary Marginal Zone Lymphomas of Ocular Adnexa are Associated with Unique Morphometric Phenotypes

Cited by 5 publications

References 27 publications

Circulating Tumor DNA Characteristics Based on Next Generation Sequencing and Its Correlation With Clinical Parameters in Patients With Lymphoma

Circulating Tumor DNA Characteristics Based on Next Generation Sequencing and Its Correlation With Clinical Parameters in Patients With Lymphoma

A comprehensive analysis of RHOA mutation positive and negative angioimmunoblastic T-cell�lymphomas by targeted deep sequencing, expression profiling and single cell digital image analysis

A Comprehensive Analysis of Rhoa Mutation Positive and Negative Angioimmunoblastic T-Cell Lymphomas By Targeted Deep Sequencing, Expression Profiling, and Single Cell Digital Image Analysis

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