From Mendelian to molecular genetics: the Xiphophorus melanoma model

Meierjohann, Svenja; Schartl, Manfred

doi:10.1016/j.tig.2006.09.013

Cited by 116 publications

(147 citation statements)

References 59 publications

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“…The Xiphophorus melanoma receptor kinase gene (XMRK) behaves as a dominant oncogene in this fish model and is a mutated derivative of the fish ortholog for the human epidermal growth factor receptor (EGFR/ErbB-1). Consistent with the activity of mammalian EGFR in melanocytes (15)(16)(17), activation of the XMRK oncoprotein leads to numerous downstream signaling cascades including, but not limited to, the RAS/RAF/MAPK and PI3-K/AKT signaling pathways (12). In addition to these signaling cascades, the transformed phenotype in Xiphophorus also involves participation of transcription factors (e.g., STAT5) and glycoproteins (e.g., osteopontin, OPN) that are intimately involved in cellular proliferation and antiapoptotic responses that characterize numerous human cancers.…”

mentioning

confidence: 76%

“…The classical, spontaneous Xiphophorus hybrid melanoma model has been studied for over 80 years and offers powerful genetic and biochemical approaches for revealing determinants of melanomagenesis (12)(13)(14). The Xiphophorus melanoma receptor kinase gene (XMRK) behaves as a dominant oncogene in this fish model and is a mutated derivative of the fish ortholog for the human epidermal growth factor receptor (EGFR/ErbB-1).…”

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confidence: 99%

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Ultraviolet A does not induce melanomas in a Xiphophorus hybrid fish model

Mitchell

Fernandez

Nairn

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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We examined the wavelength dependence of ultraviolet (UV) radiation (UVR)-induced melanoma in a Xiphophorus backcross hybrid model previously reported to be susceptible to melanoma induction by ultraviolet A (UVA) and visible light. Whereas ultraviolet B (UVB) irradiation of neonates yielded high frequencies of melanomas in pigmented fish, UVA irradiation resulted in melanoma frequencies that were not significantly different from unirradiated fish. Spontaneous and UV-induced melanoma frequencies correlated with the degree of pigmentation as expected from previous studies, and the histopathology phenotypes of the melanomas were not found in significantly different proportions in UV-treated and -untreated tumor-bearing fish. Our results support the conclusion that a brief early-life exposure to UVB radiation causes melanoma formation in this animal model. These data are consistent with an essential role for direct DNA damage, including cyclobutane dimers and (6-4) photoproducts, in the etiology of melanoma.ultraviolet B | DNA damage | cyclobutane dimer | reactive oxygen species | melanin I n the late 1980s Setlow and coworkers used genetic hybrids from interspecific crosses involving several species of the fish genus Xiphophorus to investigate the effects of UVR on the induction of cutaneous malignant melanoma (CMM) (1). These pioneering studies demonstrated that ultraviolet B (UVB) irradiation of backcross hybrids generated from a specific genetic crossing scheme induced melanomas at significant frequencies above spontaneous levels. These results were later confirmed, and the genetic basis of UVB-induced melanoma susceptibility in this cross was recognized to be the same as in the well-studied spontaneous Xiphophorus hybrid melanoma model (2). In 1993, Setlow used a different Xiphophorus interspecies cross (designated as Sp-couchianus; Fig. 1) to study the wavelength dependence of melanoma induction and reported that wavelengths in the ultraviolet A (UVA) and visible ranges were effective in inducing melanomas in first-generation backcross (BC 1 ) hybrids generated from this particular cross (3). An action spectrum for melanoma induction was proposed with maxima in the UVB (302/313 nm) and UVA (365 nm) ranges. Because UVA fluence is quantitatively much greater than UVB in sunlight incident to the earth's surface (∼10-fold), Setlow suggested that, on the basis of this action spectrum, UVA was more effective than UVB in causing melanomas in the human population (2, 4). This report had significant public health consequences; it suggested that the use of commercially available sunscreens that effectively blocked UVB but not UVA encouraged more lengthy recreational sunlight exposure and thereby increased the exposure to UVA and its associated risks. Over the past 20 years, these data have become central to the debate on the role of UVA in melanoma and the risks associated with recreational and artificial exposures to UVA wavelengths.Debate over the action spectrum for melanoma has only intensified because subsequent r...

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mentioning

confidence: 76%

mentioning

confidence: 99%

Ultraviolet A does not induce melanomas in a Xiphophorus hybrid fish model

Mitchell

Fernandez

Nairn

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…Table 3 shows five currently popular programs available for short read mapping that will be evaluated herein. To evaluate these programs, we used an X. maculatus reference transcriptome [for description of the species see section 2.7 and Kallman and Kazianis, 2006;Meierjohann and Schartl, 2006)] built from over 200 million paired-end reads sequenced from the brain, heart, and liver tissues of mature individuals using the Illumina GAIIx platform (Expression Analysis ® Inc. Durham, NC). We used the Velvet assembly package (Zerbino and Birney, 2008) to integrate the combined read set with a hash length (kmer size) of 43.…”

Section: Rna Short Read Mappingmentioning

confidence: 99%

“…The genus Xiphophorus has at least 27 species of live-bearing fishes found from northern Mexico south into Belize and Guatemala (Kallman and Kazianis, 2006). The Xiphophorus genus couples extreme genetic variability among Xiphophorus species with the capability of producing fertile interspecies hybrids that have allowed chromosomal inheritance of complex traits to be followed into individual F 1 and backcross hybrid progeny Walter and Kazianis, 2001;Meierjohann and Schartl, 2006). Using interspecies hybrids provides a unique opportunity to reveal underlying mechanisms of genetic variation.…”

Section: Snp Identification and Allele Specific Gene Expressionmentioning

confidence: 99%

Gene Expression Analysis Using RNA-Seq from Organisms Lacking Substantial Genomic Resources

Shen¹,

Garcia²,

Walter³

2011

Systems and Computational Biology - Molecular and Cellular Experimental Systems

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“…Wildtype Xiphophorine fish are insusceptible of developing neoplasia. However, certain backcrosses of swordtail (Xiphophorus helleri) with platyfish (Xiphophorus maculatus) as the recurrent parent produce offspring that can develop spontaneous neoplasia/melanoma in a Mendelian fashion [9,10]. Currently, there is only fragmentary knowledge about the histochemical and biochemical changes that accompany the very early stages of neural crest cells/premelanoblasts invasion into the developing skin of Xiphophorus hybrid fish.…”

Section: Introductionmentioning

confidence: 99%

Distribution and Extracellular Matrix Environment of Premelanoblasts during Skin Development in Xiphophorus Hybrids

Ku¹,

El-Hashash²

2017

Anat Physiol

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Neural crest cells give rise to melanoblasts that invade the dermis and epidermis to differentiate into melanocytes that can develop melanoma, which is one of the most aggressive forms of human cancer. Identification of mechanisms important for the initial development of melanoma is hampered because of the difficulty in studying them in transgenic mice with melanoma. In addition, there is only fragmentary knowledge about the histochemical and biochemical changes that accompany the very early stages of neural crest/premelanoblast invasion into the skin, which may later develop melanoma, in the naturally occurring melanoma models such as Xiphophorus fish hybrids. Herein, we used Xiphophorus hybrid fish to investigate the distribution and extracellular matrix (ECM) environment of premelanoblasts during early stages of skin development, and to test the hypothesis that there are parallels between neural crest/premelanoblast invasion and ECM changes in the early developing skin. To test this hypothesis, we investigated neural crest/premelanoblast cell distribution through development and characterize their ECM environment. We found several histochemical evidences for the correlation between this pattern of developing skin invasion by neural crest cells/premelanoblasts and the spatiotemporal relationship of extracellular matrix components that stimulate cell migration/invasion such as collagen, and others such as non-sulfated glycosaminoglycan that may facilitate cell invasion by enhancing the intercellular spaces and inhibition of extensive intercellular interactions by physically separating cells. These findings help to uncover some histochemical and biochemical changes that accompany the early stages of skin formation in Xiphophorus fish hybrids, and can also provide a conceptual framework for future mechanistic studies in this area, and for studies that use this fish hybrid as a naturally occurring melanoma model.

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From Mendelian to molecular genetics: the Xiphophorus melanoma model

Cited by 116 publications

References 59 publications

Ultraviolet A does not induce melanomas in a Xiphophorus hybrid fish model

Ultraviolet A does not induce melanomas in a Xiphophorus hybrid fish model

Gene Expression Analysis Using RNA-Seq from Organisms Lacking Substantial Genomic Resources

Distribution and Extracellular Matrix Environment of Premelanoblasts during Skin Development in Xiphophorus Hybrids

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