Histopathologic features of melanocytic tumors in &lt;i&gt;Xiphophorus&lt;/i&gt; melanoma receptor kinase (&lt;i&gt;xmrk&lt;/i&gt;)-transgenic medaka (&lt;i&gt;Oryzias latipes&lt;/i&gt;)

Sugiyama, Akihiko; Schartl, Manfred; Naruse, Kiyoshi

doi:10.1293/tox.2018-0058

Cited by 7 publications

(8 citation statements)

References 26 publications

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“…These include a few proto-oncogenes like endothelin receptor ednrbb , sarcoma viral oncogene homolog kita , Ras like estrogen regulated growth factor rerg , pleiotrophin ptn , FYN proto-oncogene fyna , erbb2 receptor tyrosine kinase 3b erbb3b . This evidence, along with previous observation that melanotic tumors are highly invasive into musculature and internal organs while xanthoerythrophoromas grow more as epiphytic nodules [42], suggests the melanoma tumors are more proliferative than xanthoerythrophoromas. Some of these proto-oncogenes are known to be induced by xmrk in Xiphophorus [43-46], culture murine cells, and most of them were reported to be involved in human melanomagenesis [43, 47-52].…”

Section: Discussionsupporting

confidence: 75%

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Transcriptional background effects on a tumor driver gene in a transgenic medaka melanoma model

Abdulsahib

Boswell

et al. 2022

Preprint

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The Xiphophorus melanoma receptor kinase gene, xmrk, is a bona fide oncogene driving melanocyte tumorigenesis of Xiphophorus fish. When ectopically expressed in medaka, it not only induces development of several pigment cell tumor types in different strains of medaka, but also induces different tumor types within the same animal, suggesting its oncogenic activity has a transcriptomic background effect. Although the central pathways that xmrk utilizes to lead to melanomagenesis are well documented, genes and genetic pathways that modulate the oncogenic effect, and alter the course of disease have not been studied so far. To understand how the genetic networks between different histocytes of xmrk-driven tumors are composed, we isolated two types of tumors, melanoma and xanthoerythrophoroma, from the same xmrk transgenic medaka individuals, established the transcriptional profiles of both xmrk-driven tumors, and compared (1) genes that are co-expressed with xmrk in both tumor types, and (2) differentially expressed genes and their associated molecular functions, between the two tumor types. Transcriptomic comparisons between the two tumor types show melanoma and xanthoerythrophoroma are characterized by transcriptional features representing varied functions, indicating distinct molecular interactions between the driving oncogene and the cell type-specific transcriptomes. Melanoma tumors exhibited gene signatures that are relevant to proliferation and invasion while xanthoerythrophoroma tumors are characterized by expression profiles related metabolism and DNA repair. We conclude the transcriptomic backgrounds, exemplified by cell-type specific genes that are downstream of xmrk effected signaling pathways, contribute the potential to change the course of tumor development and may affect overall tumor outcomes.

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Section: Discussionsupporting

confidence: 75%

“…epiphytic nodules [42], suggests the melanoma tumors are more proliferative than xanthoerythrophoromas. Some of these proto-oncogenes are known to be induced by xmrk in Xiphophorus [43][44][45][46], culture murine cells, and most of them were reported to be involved in human melanomagenesis [43,[47][48][49][50][51][52].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional background effects on a tumor driver gene in a transgenic medaka melanoma model

Abdulsahib

Boswell

et al. 2022

Preprint

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“…These include a few proto‐oncogenes like endothelin receptor ednrbb , sarcoma viral oncogene homolog kita , Ras‐like estrogen‐regulated growth factor rerg , pleiotrophin ptn , FYN proto‐oncogene fyna , and erbb2 receptor tyrosine kinase 3b erbb3b , as well as s1pr3 that is highly expressed in low‐ MITF‐ axis human melanoma. This evidence, along with the previous observation that melanotic tumors are highly invasive into musculature and internal organs while xanthophoromas grow more as epiphytic nodules (Sugiyama et al, 2019), suggests that the melanoma tumors are more proliferative than xanthophoromas. Some of these proto‐oncogenes are known to be induced by xmrk in Xiphophorus (Lu et al, 2015; Schaafhausen et al, 2013; Wellbrock & Schartl, 2000; Wellbrock et al, 2002), culture murine cells, and most of them were reported to be involved in human melanomagenesis (Bittner et al, 2000; Garraway et al, 2005; Gottesdiener et al, 2018; Lu et al, 2015; Natali et al, 1992; Ross et al, 2000; Ryu et al, 2007).…”

Section: Discussionsupporting

confidence: 66%

Transcriptional background effects on a tumor driver gene in different pigment cell types of medaka

Abdulsahib,

Boswell,

Boswell

et al. 2023

J Exp Zool Pt B

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The Xiphophorus melanoma receptor kinase gene, xmrk, is a bona fide oncogene driving melanocyte tumorigenesis of Xiphophorus fish. When ectopically expressed in medaka, it not only induces development of several pigment cell tumor types in different strains of medaka but also induces different tumor types within the same animal, suggesting its oncogenic activity has a transcriptomic background effect. Although the central pathways that xmrk utilizes to lead to melanomagenesis are well documented, genes and genetic pathways that modulate the oncogenic effect and alter the course of disease have not been studied so far. To understand how the genetic networks between different histocytes of xmrk‐driven tumors are composed, we isolated two types of tumors, melanoma and xanthoerythrophoroma, from the same xmrk transgenic medaka individuals, established the transcriptional profiles of both xmrk‐driven tumors, and compared (1) genes that are co‐expressed with xmrk in both tumor types, and (2) differentially expressed genes and their associated molecular functions, between the two tumor types. Transcriptomic comparisons between the two tumor types show melanoma and xanthoerythrophoroma are characterized by transcriptional features representing varied functions, indicating distinct molecular interactions between the driving oncogene and the cell‐type‐specific transcriptomes. Melanoma tumors exhibit gene signatures that are relevant to proliferation and invasion, while xanthoerythrophoroma tumors are characterized by expression profiles related to metabolism and DNA repair. We conclude the transcriptomic backgrounds, exemplified by cell‐type‐specific genes that are downstream of xmrk effected signaling pathways, contribute the potential to change the course of tumor development and may affect overall tumor outcomes.

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“…Previous studies have revealed that tumor histotypes depend on the genotype of the medaka strain carrying the mitf:xmrk transgene [ 8 , 10 ]. In our experiment Hd-rR displayed formation of either an orange red tumor (xanthoerythrophoroma) or a black tumor (melanoma) or both.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, Sugiyama et al. [ 10 ] compared melanocytic tumors occurring in the Carbio and HB11A strains of xmrk -transgenic medaka at 7 months post hatching and confirmed a difference in the pathological features of melanoma formation that was dependent on the genetic background.…”

Section: Introductionmentioning

confidence: 97%

Strain difference in transgene-induced tumorigenesis and suppressive effect of ionizing radiation

Dutta

Asami

Imatomi

et al. 2020

Journal of Radiation Research

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Transgenic expression in medaka of the Xiphophorus oncogene xmrk, under a pigment cell specific mitf promoter, induces hyperpigmentation and pigment cell tumors. In this study, we crossed the Hd-rR and HNI inbred strains because complete genome information is readily available for molecular and genetic analysis. We prepared an Hd-rR (p53+/−, p53−/−) and Hd-rR HNI hybrid (p53+/−) fish-based xmrk model system to study the progression of pigment cells from hyperpigmentation to malignant tumors on different genetic backgrounds. In all strains examined, most of the initial hyperpigmentation occurred in the posterior region. On the Hd-rR background, mitf:xmrk-induced tumorigenesis was less frequent in p53+/− fish than in p53−/− fish. The incidence of hyperpigmentation was more frequent in Hd-rR/HNI hybrids than in Hd-rR homozygotes; however, the frequency of malignant tumors was low, which suggested the presence of a tumor suppressor in HNI genetic background fish. The effects on tumorigenesis in xmrk-transgenic immature medaka of a single 1.3 Gy irradiation was assessed by quantifying tumor progression over 4 consecutive months. The results demonstrate that irradiation has a different level of suppressive effect on the frequency of hyperpigmentation in purebred Hd-rR compared with hybrids.

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Histopathologic features of melanocytic tumors in <i>Xiphophorus</i> melanoma receptor kinase (<i>xmrk</i>)-transgenic medaka (<i>Oryzias latipes</i>)

Cited by 7 publications

References 26 publications

Transcriptional background effects on a tumor driver gene in a transgenic medaka melanoma model

Transcriptional background effects on a tumor driver gene in a transgenic medaka melanoma model

Transcriptional background effects on a tumor driver gene in different pigment cell types of medaka

Strain difference in transgene-induced tumorigenesis and suppressive effect of ionizing radiation

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