Shared hotspot mutations in oncogenes position dogs as an unparalleled comparative model for precision therapeutics.
Shared hotspot mutations in oncogenes position dogs as an unparalleled comparative model for precision therapeutics.
复制标题
DOI：
10.1038/s41598-023-37505-2
复制
发表时间：
2023-07-06
影响因子：
4.6
通讯作者：
Zhao, Shaying
中科院分区：
文献类型：
--
作者：
Rodrigues, Lucas;Watson, Joshua;Feng, Yuan;Lewis, Benjamin;Harvey, Garrett;Post, Gerald;Megquier, Kate;White, Michelle E.;Lambert, Lindsay;Miller, Aubrey;Lopes, Christina;Zhao, Shaying
自然发生的犬类癌症与人类癌症有显着的相似之处。为了更好地了解这些相似性，我们调查了来自96个品种的671只客户拥有的狗，其中有23种常见肿瘤类型，包括那些突变谱未知（肛门囊癌和神经内分泌癌）或研究不足（甲状腺癌，软组织肉瘤和肝细胞癌）。我们发现了50个成熟的癌基因和肿瘤抑制基因的突变，并将它们与人类癌症中报道的突变进行了比较。与人类癌症一样，TP53是最常见的突变基因，在22.5%的犬肿瘤中检测到。犬肿瘤与人类肿瘤在包括PIK3CA、KRAS、NRAS、BRAF、KIT和EGFR在内的癌基因中共享突变热点。与肿瘤类型显著相关的热点突变包括血管肉瘤中的NRAS G61 R和PIK3CA H1047 R、肺癌中的ERBB 2 V659 E和尿路上皮癌中的BRAF V588 E（相当于人类中的V600 E）。我们的研究结果更好地将犬作为人类癌症的转化模型，以研究广泛的靶向治疗。
Naturally occurring canine cancers have remarkable similarities to their human counterparts. To better understand these similarities, we investigated 671 client-owned dogs from 96 breeds with 23 common tumor types, including those whose mutation profile are unknown (anal sac carcinoma and neuroendocrine carcinoma) or understudied (thyroid carcinoma, soft tissue sarcoma and hepatocellular carcinoma). We discovered mutations in 50 well-established oncogenes and tumor suppressors, and compared them to those reported in human cancers. As in human cancer, TP53 is the most commonly mutated gene, detected in 22.5% of canine tumors overall. Canine tumors share mutational hotspots with human tumors in oncogenes including PIK3CA, KRAS, NRAS, BRAF, KIT and EGFR. Hotspot mutations with significant association to tumor type include NRAS G61R and PIK3CA H1047R in hemangiosarcoma, ERBB2 V659E in pulmonary carcinoma, and BRAF V588E (equivalent of V600E in humans) in urothelial carcinoma. Our findings better position canines as a translational model of human cancer to investigate a wide spectrum of targeted therapies.
登录
查看更多内容
影响因子：
16.6
作者：
Alsaihati BA;Ho KL;Watson J;Feng Y;Wang T;Dobbin KK;Zhao S
通讯作者：
Zhao S
DOI：
10.1016/j.cvsm.2019.04.011
发表时间：
2019-09-01
影响因子：
1.9
作者：
Katogiritis, Anna;Khanna, Chand
通讯作者：
Khanna, Chand
影响因子：
3.7
作者：
Paoloni M;Webb C;Mazcko C;Cherba D;Hendricks W;Lana S;Ehrhart EJ;Charles B;Fehling H;Kumar L;Vail D;Henson M;Childress M;Kitchell B;Kingsley C;Kim S;Neff M;Davis B;Khanna C;Trent J
通讯作者：
Trent J
DOI：
10.1093/database/bay119
发表时间：
2018-11-06
影响因子：
5.8
作者：
Hunt, Sarah E.;McLaren, William;Cunningham, Fiona
通讯作者：
Cunningham, Fiona
影响因子：
4.3
作者：
Halaban R;Zhang W;Bacchiocchi A;Cheng E;Parisi F;Ariyan S;Krauthammer M;McCusker JP;Kluger Y;Sznol M
通讯作者：
Sznol M