Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Department of Pathobiology, University of Guelph, 50 Stone Road E., Guelph, ON N1G 2W1, Canada.
Dis Model Mech. 2021 Jul 1;14(7). doi: 10.1242/dmm.049044. Epub 2021 Jul 23.
Angiosarcoma (AS) is a highly aggressive tumor of blood and lymphatic vessels in humans that shares many similarities with spontaneously occurring hemangiosarcoma (HSA) in dogs and cats. To investigate the genetic suitability of HSA as a model for AS, we sequenced ∼1000 cancer genes in 41 cases of HSA and matched germline tissue: 15 canine visceral HSAs, 13 canine skin HSAs and 13 feline skin HSAs. Analysis of visceral HSAs from dogs presenting with concurrent splenic and cardiac neoplasms showed that the tumors were not independent primaries, consistent with the highly metastatic nature of HSA. Comparison of HSA to AS revealed that several driver genes were recurrently mutated in both species, such as TP53, PIK3CA, ATRX, GRIN2A and LRP1B. Similar to AS, a UV mutational signature was found in a subset of canine cutaneous HSAs and both species show differing mutational profiles between tissue sites. Our characterization of canine and feline HSA demonstrates many important parallels to AS and provides hope that future studies on these cancers will benefit of all three species.
血管肉瘤（AS）是一种人类血液和淋巴管的高度侵袭性肿瘤，与犬猫自发性发生的血管肉瘤（HSA）有许多相似之处。为了研究 HSA 是否适合作为 AS 的模型，我们对 41 例 HSA 及其相应的种系组织进行了约 1000 个癌症基因的测序：15 例犬内脏 HSA、13 例犬皮肤 HSA 和 13 例猫皮肤 HSA。对同时存在脾脏和心脏肿瘤的犬内脏 HSA 的分析表明，这些肿瘤不是独立的原发性肿瘤，这与 HSA 的高度转移性一致。HSA 与 AS 的比较表明，两种物种中都有几个驱动基因经常发生突变，如 TP53、PIK3CA、ATRX、GRIN2A 和 LRP1B。与 AS 相似，在一组犬皮肤 HSA 中发现了紫外线突变特征，两种物种在组织部位之间显示出不同的突变特征。我们对犬和猫 HSA 的描述表明，与 AS 有许多重要的相似之处，并希望未来对这些癌症的研究将受益于这三个物种。
