Genomic analysis reveals shared genes and pathways in human and canine angiosarcoma
| Autor: | Sharadha Sakthikumar, Rachael Thomas, Aaron L. Sarver, Jessica Alföldi, Ingegerd Elvers, Luke B. Borst, Jaime F. Modiano, Mitzi Lewellen, Ashley J. Graef, Chao Wang, Elinor K. Karlsson, Jong Hyuk Kim, Kate Megquier, Noriko Tonomura, Kerstin Lindblad-Toh, Milcah C. Scott, Ross Swofford, Matthew Breen, Jason Turner-Maier, Corrie A. Painter, Jeremy Johnson, Michele Koltookian |
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| Rok vydání: | 2019 |
| Předmět: |
Genetics
Oncogene 040301 veterinary sciences Somatic cell Cadherin RNA 04 agricultural and veterinary sciences Biology digestive system diseases 3. Good health 0403 veterinary science 03 medical and health sciences 0302 clinical medicine CDKN2A 030220 oncology & carcinogenesis Angiosarcoma neoplasms Gene Exome sequencing |
| DOI: | 10.1101/570879 |
| Popis: | Angiosarcoma is a highly aggressive cancer of blood vessel-forming cells with high fatality and few effective treatment options. It is both rare and heterogenous, making large, well powered genomic studies nearly impossible. In dogs, angiosarcoma is common, with breeds like the golden retriever carrying heritable genetic factors that put them at very high risk. If the clinical similarity of canine and human angiosarcoma reflects shared genomic etiology, dogs could be a critically needed model for advancing angiosarcoma research. We assessed the genomic landscape of canine angiosarcoma via whole exome sequencing (47 golden retriever angiosarcomas) and RNA sequencing (74 angiosarcomas from multiple breeds). The predominant mutational signature was the age-associated deamination of cytosine to thymine, and somatic coding mutations occurred most frequently in the tumor suppressorTP53(59.6% of cases) as well as two genes in the PI3K pathway: the oncogenePIK3CA(29.8%) and its regulatory subunitPIK3R1(8.5%). We compared the canine data to human data recently released by The Angiosarcoma Project, and found the same genes and many of the same pathways significantly enriched for somatic mutations, most notably protein kinases, glycoproteins, fibronectin Type III domains, EGF-like domains, and cell adhesion proteins such as cadherins. As in human angiosarcoma,CDKN2A/Bwas recurrently deleted andVEGFA, KDR, and KITrecurrently gained. Canine angiosarcoma closely models human angiosarcoma on a genomic level, and is a powerful tool for investigating the pathogenesis of this devastating disease. |
| Databáze: | OpenAIRE |
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