The Xiphophorus Genetic Stock Center, Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX, USA.
Physiological Chemistry, Biozentrum, University of Würzburg, Würzburg, Germany.
Pigment Cell Melanoma Res. 2018 Jul;31(4):496-508. doi: 10.1111/pcmr.12686. Epub 2018 Jan 29.
Comparative analysis of human and animal model melanomas can uncover conserved pathways and genetic changes that are relevant for the biology of cancer cells. Spontaneous melanoma in Xiphophorus interspecies backcross hybrid progeny may be informative in identifying genes and functional pathways that are similarly related to melanoma development in all vertebrates, including humans. To assess functional pathways involved in the Xiphophorus melanoma, we performed gene expression profiling of the melanomas produced in interspecies BC and successive backcross generations (i.e., BC ) of the cross: X. hellerii × [X. maculatus Jp 163 A × X. hellerii]. Using RNA-Seq, we identified genes that are transcriptionally co-expressed with the driver oncogene, xmrk. We determined functional pathways in the fish melanoma that are also present in human melanoma cohorts that may be related to dedifferentiation based on the expression levels of pigmentation genes. Shared pathways between human and Xiphophorus melanomas are related to inflammation, cell migration, cell proliferation, pigmentation, cancer development, and metastasis. Our results suggest xmrk co-expressed genes are associated with dedifferentiation and highlight these signaling pathways as playing important roles in melanomagenesis.
对人类和动物模型黑色素瘤的比较分析可以揭示与癌症生物学相关的保守途径和遗传变化。剑尾鱼种间回交杂种后代的自发性黑色素瘤可能有助于确定与所有脊椎动物（包括人类）黑色素瘤发展类似相关的基因和功能途径。为了评估剑尾鱼黑色素瘤中涉及的功能途径，我们对种间回交和连续回交后代（即 BC ）中产生的黑色素瘤进行了基因表达谱分析：X. hellerii × [X. maculatus Jp 163 A × X. hellerii]。使用 RNA-Seq，我们鉴定了与驱动致癌基因 xmrk 转录共表达的基因。我们确定了鱼类黑色素瘤中的功能途径，这些途径也存在于人类黑色素瘤队列中，可能与基于色素基因表达水平的去分化有关。人类和剑尾鱼黑色素瘤之间的共享途径与炎症、细胞迁移、细胞增殖、色素沉着、癌症发展和转移有关。我们的结果表明，xmrk 共表达的基因与去分化有关，并强调这些信号通路在黑色素瘤发生中起着重要作用。
