Comprehensive polymerase chain reaction assay for detection of pathogenic DNA in lymphoproliferative disorders of the ocular adnexa

Usui, Yoshihiko; Rao, Narsing A.; Takase, Hiroshi; Tsubota, Kinya; Umazume, Kazuhiko; Diaz-Aguilar, Daniel; Kezuka, Takeshi; Mochizuki, Manabu; Gotô, Hiroshi; Sugita, Sunao

doi:10.1038/srep36621

Cited by 16 publications

(18 citation statements)

References 32 publications

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“…Finally, since the short arm of chromosome 6 carries the major histocompatibility complex (Additional file 2 : Table S7) which encodes HLA class I antigens, mandatory for tumor cells to be recognized by cytotoxic T cells, the two monosomic cases (DSRCT3 and 7) are expected to show characteristics of immunoescape [ 32 ]. Further strength to a deficient immune response in these two cases is given by the loss of the following genes located on short arm of chromosome 6: proteasome subunit beta 8 ( PSMB8 ) and proteasome subunit beta 9 ( PSMB9 ), transporter 1, ATP-binding cassette subfamily B member ( TAP1 ) transporter 2, ATP-binding cassette subfamily B member ( TAP2 ), and TAP-binding protein ( TAPBP ) associated with antigen presentation; and interferon regulatory factor 4 ( IRF4 , also named MUM1 ) recently demonstrated to be fundamental in generation of Type 1 T helper (Th1) response [ 33 ].…”

Section: Resultsmentioning

confidence: 99%

The genomics of desmoplastic small round cell tumor reveals the deregulation of genes related to DNA damage response, epithelial–mesenchymal transition, and immune response

Devecchi

Cecco

Dugo

et al. 2018

Cancer Communications

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BackgroundDesmoplastic small round cell tumor (DSRCT) is a rare, aggressive, and poorly investigated simple sarcoma with a low frequency of genetic deregulation other than an Ewing sarcoma RNA binding protein 1 (EWSR1)-Wilm’s tumor suppressor (WT1) translocation. We used whole-exome sequencing to interrogate six consecutive pre-treated DSRCTs whose gene expression was previously investigated.MethodsDNA libraries were prepared from formalin-fixed, paraffin-embedded archival tissue specimens following the Agilent SureSelectXT2 target enrichment protocol and sequenced on Illumina NextSeq 500. Raw sequence data were aligned to the reference genome with Burrows–Wheeler Aligner algorithm. Somatic mutations and copy number alterations (CNAs) were identified using MuTect2 and EXCAVATOR2, respectively. Biological functions associated with altered genes were investigated through Ingenuity Pathway Analysis (IPA) software.ResultsA total of 137 unique somatic mutations were identified: 133 mutated genes were case-specific, and 2 were mutated in two cases but in different positions. Among the 135 mutated genes, 27% were related to two biological categories: DNA damage-response (DDR) network that was also identified through IPA and mesenchymal–epithelial reverse transition (MErT)/epithelial–mesenchymal transition (EMT) already demonstrated to be relevant in DSRCT. The mutated genes in the DDR network were involved in various steps of transcription and particularly affected pre-mRNA. Half of these genes encoded RNA-binding proteins or DNA/RNA-binding proteins, which were recently recognized as a new class of DDR players. CNAs in genes/gene families, involved in MErT/EMT and DDR, were recurrent across patients and mostly segregated in the MErT/EMT category. In addition, recurrent gains of regions in chromosome 1 involving many MErT/EMT gene families and loss of one arm or the entire chromosome 6 affecting relevant immune-regulatory genes were recorded.ConclusionsThe emerging picture is an extreme inter-tumor heterogeneity, characterized by the concurrent deregulation of the DDR and MErT/EMT dynamic and plastic programs that could favour genomic instability and explain the refractory DSRCT profile.Electronic supplementary materialThe online version of this article (10.1186/s40880-018-0339-3) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

The genomics of desmoplastic small round cell tumor reveals the deregulation of genes related to DNA damage response, epithelial–mesenchymal transition, and immune response

Devecchi

Cecco

Dugo

et al. 2018

Cancer Communications

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“…PCR-based reports have documented an extreme range of HHV-6 positivity with 0–100% of blood/bone marrow/lymph nodes from cases testing positive. For instance, Usui et al detected HHV-6 in up to 6.7% of ocular MALT tissues, while an earlier team documented a positive rate of 28.6% ( 31 , 38 ). Among some studies, the ability to draw conclusions is limited by small sample sizes, even when the HHV-6 species is typed, the viral load is quantified, and types of lymphoma are differentiated ( 8 , 12 , 36 ).…”

Section: Hhv-6 As the Sole Infectious Agent In Cancers: By System/sitmentioning

confidence: 99%

Human Herpesvirus 6 and Malignancy: A Review

et al. 2018

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In order to determine the role of human herpesvirus 6 (HHV-6) in human disease, several confounding factors, including methods of detection, types of controls, and the ubiquitous nature of the virus, must be considered. This is particularly problematic in the case of cancer, in which rates of detection vary greatly among studies. To determine what part, if any, HHV-6 plays in oncogenesis, a review of the literature was performed. There is evidence that HHV-6 is present in certain types of cancer; however, detection of the virus within tumor cells is insufficient for assigning a direct role of HHV-6 in tumorigenesis. Findings supportive of a causal role for a virus in cancer include presence of the virus in a large proportion of cases, presence of the virus in most tumor cells, and virus-induced in-vitro cell transformation. HHV-6, if not directly oncogenic, may act as a contributory factor that indirectly enhances tumor cell growth, in some cases by cooperation with other viruses. Another possibility is that HHV-6 may merely be an opportunistic virus that thrives in the immunodeficient tumor microenvironment. Although many studies have been carried out, it is still premature to definitively implicate HHV-6 in several human cancers. In some instances, evidence suggests that HHV-6 may cooperate with other viruses, including EBV, HPV, and HHV-8, in the development of cancer, and HHV-6 may have a role in such conditions as nodular sclerosis Hodgkin lymphoma, gastrointestinal cancer, glial tumors, and oral cancers. However, further studies will be required to determine the exact contributions of HHV-6 to tumorigenesis.

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“…However, similar results were not obtained for the other miRNAs. Orbital MALT lymphoma is rarely caused by Helicobacter pylori [51,52]. Therefore, the difference in miRNA profile between orbital MALT lymphoma and gastric MALT lymphoma may be attributed to the different characteristics of these two distinct types of MALT lymphoma and/or usage of different assays.…”

Section: Discussionmentioning

confidence: 99%

Distinctive Tissue and Serum MicroRNA Profile of IgG4-Related Ophthalmic Disease and MALT Lymphoma

Nezu

Usui

Asakage

et al. 2020

JCM

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The molecular pathogenesis of orbital lymphoproliferative disorders, such as immunoglobulin G4-related ophthalmic disease (IgG4-ROD) and orbital mucosa-associated lymphoid tissue (MALT) lymphoma, remains essentially unknown. Differentiation between the two disorders, which is important since the work-up and treatment can vary greatly, is often challenging due to the lack of specific biomarkers. Although miRNAs play an important role in the regulation of carcinogenesis and inflammation, the relationship between miRNA and orbital lymphoproliferative diseases remains unknown. We performed a comprehensive analysis of 2565 miRNAs from biopsy and serum specimens of 17 cases with IgG4-ROD, where 21 cases with orbital MALT lymphoma were performed. We identified specific miRNA signatures and their miRNA target pathways, as well as the network analysis for IgG4-ROD and orbital MALT lymphoma. Machine-learning analysis identified miR-202-3p and miR-7112-3p as the best discriminators of IgG4-ROD and orbital MALT lymphoma, respectively. Enrichment analyses of biological pathways showed that the longevity-regulating pathway in IgG4-ROD and the mitogen-activated protein kinase (MAPK) signaling pathway in orbital MALT lymphoma was most enriched by target genes of downregulated miRNAs. This is the first evidence of miRNA profiles of biopsy and serum specimens of patients with IgG4-ROD and orbital MALT lymphoma. These data will be useful for developing diagnostic and therapeutic interventions, as well as elucidating the pathogenesis of these disorders.

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Comprehensive polymerase chain reaction assay for detection of pathogenic DNA in lymphoproliferative disorders of the ocular adnexa

Cited by 16 publications

References 32 publications

The genomics of desmoplastic small round cell tumor reveals the deregulation of genes related to DNA damage response, epithelial–mesenchymal transition, and immune response

The genomics of desmoplastic small round cell tumor reveals the deregulation of genes related to DNA damage response, epithelial–mesenchymal transition, and immune response

Human Herpesvirus 6 and Malignancy: A Review

Distinctive Tissue and Serum MicroRNA Profile of IgG4-Related Ophthalmic Disease and MALT Lymphoma

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