Germline gene fusions across species reveal the chromosomal instability regions and cancer susceptibility
Bo-Wen Zhou,
Qing-Qin Wu,
David H. Mauki,
Xuan Wang,
Shu-Run Zhang,
Ting-Ting Yin,
Fang-Liang Chen,
Chao Li,
Yan-Hu Liu,
Guo-Dong Wang,
Ya-Ping Zhang
Affiliations
Bo-Wen Zhou
State Key Laboratory of Genetic Resources and Evolution & Yunnan Laboratory of Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China
Qing-Qin Wu
School of Ecology and Environmental Sciences, Yunnan University, Kunming, Yunnan 650500, China
David H. Mauki
Institute of Neurological Disease, National-Local Joint Engineering Research Center of Translational Medicine, State Key Lab of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
Xuan Wang
State Key Laboratory of Genetic Resources and Evolution & Yunnan Laboratory of Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China
Shu-Run Zhang
State Key Laboratory of Genetic Resources and Evolution & Yunnan Laboratory of Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China
Ting-Ting Yin
State Key Laboratory of Genetic Resources and Evolution & Yunnan Laboratory of Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China
Fang-Liang Chen
Kunming Police Dog Base of the Ministry of Public Security, Kunming, Yunnan 650204, China
Chao Li
State Key Laboratory for Conservation and Utilization of Bio-Resource, Yunnan University, Kunming, Yunnan 650500, China
Yan-Hu Liu
State Key Laboratory of Genetic Resources and Evolution & Yunnan Laboratory of Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China; Corresponding author
Guo-Dong Wang
State Key Laboratory of Genetic Resources and Evolution & Yunnan Laboratory of Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China; Corresponding author
Ya-Ping Zhang
State Key Laboratory of Genetic Resources and Evolution & Yunnan Laboratory of Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China; Corresponding author
Summary: The canine transmissible venereal tumor (CTVT) is a clonal cell-mediated cancer with a long evolutionary history and extensive karyotype rearrangements in its genome. However, little is known about its genetic similarity to human tumors. Here, using multi-omics data we identified 11 germline gene fusions (GGFs) in CTVT, which showed higher genetic susceptibility than others. Additionally, we illustrate a mechanism of a complex gene fusion of three gene segments (HSD17B4-DMXL1-TNFAIP8) that we refer to “greedy fusion”. Our findings also provided evidence that expressions of GGFs are downregulated during the tumor regressive phase, which is associated with DNA methylation level. This study presents a comprehensive landscape of gene fusions (GFs) in CTVT, which offers a valuable genetic resource for exploring potential genetic mechanisms underlying the development of cancers in both dogs and humans.
