Comparison against 186 canid whole-genome sequences reveals survival strategies of an ancient clonally transmissible canine tumor.
Comparison against 186 canid whole-genome sequences reveals survival strategies of an ancient clonally transmissible canine tumor.
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DOI：
10.1101/gr.190314.115
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发表时间：
2015-11
期刊：
影响因子：
7
通讯作者：
Ostrander EA
中科院分区：
文献类型：
--
作者：
Decker B;Davis BW;Rimbault M;Long AH;Karlins E;Jagannathan V;Reiman R;Parker HG;Drögemüller C;Corneveaux JJ;Chapman ES;Trent JM;Leeb T;Huentelman MJ;Wayne RK;Karyadi DM;Ostrander EA
犬传染性性病瘤（CTVT）是一种寄生性癌症克隆，通过恶性细胞的性转移已经繁殖了数千年。人们对将一个古老的肿瘤转化为世界上已知的最古老的持续繁殖的体细胞谱系的机制知之甚少。我们创建了现有最大的犬全基因组变异目录，并将其与两个CTVT基因组序列进行比较，从而将来自创始人基因组的等位基因与必须驱动克隆遗传性的体细胞突变分开。我们发现CTVT已经经历了持续适应其可传播的同种异体移植物生态位，在免疫监视的每一步都有重叠突变，特别是自身抗原呈递和细胞凋亡。我们还确定了肿瘤发生和免疫相关基因的时间早期体细胞突变，这些基因可能是克隆遗传性的关键启动子。因此，我们提供了第一次深入了解特定的基因组畸变的基础CTVT的顽强毅力在世界各地的犬科动物。
Canine transmissible venereal tumor (CTVT) is a parasitic cancer clone that has propagated for thousands of years via sexual transfer of malignant cells. Little is understood about the mechanisms that converted an ancient tumor into the world's oldest known continuously propagating somatic cell lineage. We created the largest existing catalog of canine genome-wide variation and compared it against two CTVT genome sequences, thereby separating alleles derived from the founder's genome from somatic mutations that must drive clonal transmissibility. We show that CTVT has undergone continuous adaptation to its transmissible allograft niche, with overlapping mutations at every step of immunosurveillance, particularly self-antigen presentation and apoptosis. We also identified chronologically early somatic mutations in oncogenesis- and immune-related genes that may represent key initiators of clonal transmissibility. Thus, we provide the first insights into the specific genomic aberrations that underlie CTVT's dogged perseverance in canids around the world.