Genomic restructuring in the Tasmanian devil facial tumour: chromosome painting and gene mapping provide clues to evolution of a transmissible tumour.
Genomic restructuring in the Tasmanian devil facial tumour: chromosome painting and gene mapping provide clues to evolution of a transmissible tumour.
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DOI：
10.1371/journal.pgen.1002483
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Graves JA
中科院分区：
文献类型：
--
作者：
Deakin JE;Bender HS;Pearse AM;Rens W;O'Brien PC;Ferguson-Smith MA;Cheng Y;Morris K;Taylor R;Stuart A;Belov K;Amemiya CT;Murchison EP;Papenfuss AT;Graves JA
魔鬼面部肿瘤病（DFTD）是一种致命的传染性恶性肿瘤，威胁着世界上最大的有袋类食肉动物塔斯马尼亚魔鬼的灭绝。DFTD于1996年首次被发现，它对野生魔鬼的数量产生了灾难性的影响，此后为了解和控制这种疾病而进行的大量研究表明，这种肿瘤是一种通过同种异体移植传播的克隆细胞系。我们使用染色体彩绘和基因定位来解构DFTD核型，并确定致癌作用中涉及的染色体和基因重排。三种不同DFTD肿瘤株的染色体彩绘确定了标记染色体的起源，并提供了DFTD核型重排的一般概述。通过荧光原位杂交对105个BAC克隆进行作图，提供了DFTD菌株中基因组重排的更精细水平的分辨率。我们的研究结果表明，只有有限的区域的基因组，主要是染色体1和X，在DFTD重排。DFTD中重排的区域在不同的有袋类动物之间也高度重排。菌株之间的差异是有限的，反映了DFTD异常稳定的性质。最后，我们的魔鬼和肿瘤核型的详细地图提供了一个物理框架，为未来的基因组调查DFTD。世界上最大的食肉有袋类动物塔斯马尼亚魔鬼，由于出现了一种致命的传染性肿瘤--魔鬼面部肿瘤病（DFTD），正面临灭绝的威胁。遗传多样性的严重丧失使魔鬼在咬和下颌摔跤时容易通过移植或移植细胞来传播肿瘤细胞。DFTD肿瘤的初步研究显示肿瘤染色体之间的重排，有几个缺失的染色体和四个未知来源的额外标记染色体。从那时起，新的疾病菌株出现了，似乎是从原来的菌株衍生出来的。由于没有关于正常魔鬼染色体上基因位置的先验信息，DFTD中染色体重排表征的必要第一步是构建正常魔鬼基因组的图谱。这使我们能够阐明三个DFTD菌株的染色体重排。在此过程中，我们确定了标记染色体的起源，并比较了三种菌株，以确定基因组的哪些区域参与了正在进行的肿瘤演变。有趣的是，菌株之间的重排仅限于特定的基因组区域，这表明这种独特的癌症具有不寻常的稳定性。因此，这项研究是了解DFTD遗传学的重要第一步。
Devil facial tumour disease (DFTD) is a fatal, transmissible malignancy that threatens the world's largest marsupial carnivore, the Tasmanian devil, with extinction. First recognised in 1996, DFTD has had a catastrophic effect on wild devil numbers, and intense research efforts to understand and contain the disease have since demonstrated that the tumour is a clonal cell line transmitted by allograft. We used chromosome painting and gene mapping to deconstruct the DFTD karyotype and determine the chromosome and gene rearrangements involved in carcinogenesis. Chromosome painting on three different DFTD tumour strains determined the origins of marker chromosomes and provided a general overview of the rearrangement in DFTD karyotypes. Mapping of 105 BAC clones by fluorescence in situ hybridisation provided a finer level of resolution of genome rearrangements in DFTD strains. Our findings demonstrate that only limited regions of the genome, mainly chromosomes 1 and X, are rearranged in DFTD. Regions rearranged in DFTD are also highly rearranged between different marsupials. Differences between strains are limited, reflecting the unusually stable nature of DFTD. Finally, our detailed maps of both the devil and tumour karyotypes provide a physical framework for future genomic investigations into DFTD. The world's largest carnivorous marsupial, the Tasmanian devil, is threatened with extinction due to the emergence of devil facial tumour disease (DFTD), a fatal transmissible tumour. Critical loss of genetic diversity has rendered the devil vulnerable to transmission of tumour cells by grafting or transplanting the cells while biting and jaw wrestling. Initial studies of DFTD tumours revealed rearrangements among tumour chromosomes, with several missing chromosomes and four additional marker chromosomes of unknown origin. Since then, new strains of the disease have emerged and appear to be derived from the original strain. With no prior information available regarding the location of genes on normal devil chromosomes, a necessary first step towards characterisation of chromosome rearrangements in DFTD was to construct a map of the normal devil genome. This enabled us to elucidate the chromosome rearrangements in three DFTD strains. In doing so we determined the origin of the marker chromosomes and compared the three strains to determine which areas of the genome are involved in ongoing tumour evolution. Interestingly, rearrangements between strains are limited to particular genomic regions, demonstrating the unusual stability of this unique cancer. This study is therefore an important first step towards understanding the genetics of DFTD.
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DOI：
10.1073/pnas.0712345105
发表时间：
2008-03-18
影响因子：
11.1
作者：
Jones, Sian;Chen, Wei-dong;Markowitz, Sanford D.
通讯作者：
Markowitz, Sanford D.