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Transmissible dog cancer genome reveals the origin and history of an ancient cell lineage

ABSTRACT: Whole genome sequences of two canine transmissible venereal tumours (CTVTs) and their hosts derived from Australia and Brazil

PROVIDER: PRJEB5068 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR466751.fastq.gz	Fastqsanger.gz
	ERR466751_1.fastq.gz	Fastqsanger.gz
	ERR466751_2.fastq.gz	Fastqsanger.gz
	ERR466752.fastq.gz	Fastqsanger.gz
	ERR466752_1.fastq.gz	Fastqsanger.gz

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Transmissible [corrected] dog cancer genome reveals the origin and history of an ancient cell lineage.

Project description:Canine transmissible venereal tumor (CTVT) is the oldest known somatic cell lineage. It is a transmissible cancer that propagates naturally in dogs. We sequenced the genomes of two CTVT tumors and found that CTVT has acquired 1.9 million somatic substitution mutations and bears evidence of exposure to ultraviolet light. CTVT is remarkably stable and lacks subclonal heterogeneity despite thousands of rearrangements, copy-number changes, and retrotransposon insertions. More than 10,000 genes carry nonsynonymous variants, and 646 genes have been lost. CTVT first arose in a dog with low genomic heterozygosity that may have lived about 11,000 years ago. The cancer spawned by this individual dispersed across continents about 500 years ago. Our results provide a genetic identikit of an ancient dog and demonstrate the robustness of mammalian somatic cells to survive for millennia despite a massive mutation burden.

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Project description:Devil facial tumour disease 1 and 2 (DFT1 and DFT2) are two genetically distinct transmissible cancers endangering the survival of the Tasmanian devil (Sarcophilus harrisii). DFT1 first arose from a cell of the Schwann cell lineage, however, the tissue-of-origin of the recently discovered DFT2 cancer remains unknown. Here we have performed mRNA and protein expression analyses to show that variation in expression patterns between DFT1 and DFT2 tumours is low. Furthermore, DFT2 cells express a range of markers associated with Schwann cell differentiation, suggesting a similar tissue-of-origin to DFT1 tumours. These findings suggest that devils may be predisposed to transmissible cancers of Schwann cell origin. The emergence of these two unique cancers presents an unprecedented opportunity to gain insight into cancer development in animal species.

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