Canine tumor mutational burden is correlated with TP53 mutation across tumor types and breeds.
Canine tumor mutational burden is correlated with TP53 mutation across tumor types and breeds.
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DOI：
10.1038/s41467-021-24836-9
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发表时间：
2021-08-03
影响因子：
16.6
通讯作者：
Zhao S
中科院分区：
文献类型：
--
作者：
Alsaihati BA;Ho KL;Watson J;Feng Y;Wang T;Dobbin KK;Zhao S
自发性犬癌是有价值的，但相对研究和利用较少的模型。为了加强它们的使用，我们重新分析了发表的684例7种常见肿瘤和35种肿瘤的完整外显子组和基因组测序数据，并进行了严格的质量控制和品种验证。我们的结果表明，犬类肿瘤的改变与肿瘤类型有关，但可能与品种无关。每种肿瘤类型的主要途径改变也在人类同类肿瘤中发现(例如，乳腺癌中的PI3K和骨肉瘤中的P53)。乳腺肿瘤和胶质瘤的肿瘤突变负荷较低(中位数 和lt； 突变/Mb)，而口腔黑色素瘤、骨肉瘤和血管肉瘤的肿瘤突变负荷较高(中位数 ≥ 1突变/Mb)。在肿瘤类型和品种中，TMB与TP53的突变有关，但与突变最多的基因PIK3CA无关。金毛猎犬具有TMB相关和骨肉瘤丰富的突变特征。在这里，我们提供了主要肿瘤类型和品种的犬类突变的快照。对犬类肿瘤的基因组研究已经针对单个癌症类型或犬种进行了。在这里，作者分析了多个品种和癌症类型的犬类肿瘤基因组数据，发现突变负担与TP53突变有关，金毛猎犬的特定特征得到了丰富。
Spontaneous canine cancers are valuable but relatively understudied and underutilized models. To enhance their usage, we reanalyze whole exome and genome sequencing data published for 684 cases of >7 common tumor types and >35 breeds, with rigorous quality control and breed validation. Our results indicate that canine tumor alteration landscape is tumor type-dependent, but likely breed-independent. Each tumor type harbors major pathway alterations also found in its human counterpart (e.g., PI3K in mammary tumor and p53 in osteosarcoma). Mammary tumor and glioma have lower tumor mutational burden (TMB) (median < 0.5 mutations per Mb), whereas oral melanoma, osteosarcoma and hemangiosarcoma have higher TMB (median ≥ 1 mutations per Mb). Across tumor types and breeds, TMB is associated with mutation of TP53 but not PIK3CA, the most mutated genes. Golden Retrievers harbor a TMB-associated and osteosarcoma-enriched mutation signature. Here, we provide a snapshot of canine mutations across major tumor types and breeds. Genomic studies of canine tumours have been done for individual cancer types or dog breeds. Here the authors analyse canine tumour genomics data across multiple breeds and cancer types, finding that mutational burden is associated with TP53 mutations and that Golden Retrievers are enriched for particular signatures.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
30.8
作者：
da Silva Almeida AC;Abate F;Khiabanian H;Martinez-Escala E;Guitart J;Tensen CP;Vermeer MH;Rabadan R;Ferrando A;Palomero T
通讯作者：
Palomero T
影响因子：
50.3
作者：
Berger AC;Korkut A;Kanchi RS;Hegde AM;Lenoir W;Liu W;Liu Y;Fan H;Shen H;Ravikumar V;Rao A;Schultz A;Li X;Sumazin P;Williams C;Mestdagh P;Gunaratne PH;Yau C;Bowlby R;Robertson AG;Tiezzi DG;Wang C;Cherniack AD;Godwin AK;Kuderer NM;Rader JS;Zuna RE;Sood AK;Lazar AJ;Ojesina AI;Adebamowo C;Adebamowo SN;Baggerly KA;Chen TW;Chiu HS;Lefever S;Liu L;MacKenzie K;Orsulic S;Roszik J;Shelley CS;Song Q;Vellano CP;Wentzensen N;Cancer Genome Atlas Research Network;Weinstein JN;Mills GB;Levine DA;Akbani R
通讯作者：
Akbani R
影响因子：
16.6
作者：
Behjati S;Tarpey PS;Haase K;Ye H;Young MD;Alexandrov LB;Farndon SJ;Collord G;Wedge DC;Martincorena I;Cooke SL;Davies H;Mifsud W;Lidgren M;Martin S;Latimer C;Maddison M;Butler AP;Teague JW;Pillay N;Shlien A;McDermott U;Futreal PA;Baumhoer D;Zaikova O;Bjerkehagen B;Myklebost O;Amary MF;Tirabosco R;Van Loo P;Stratton MR;Flanagan AM;Campbell PJ
通讯作者：
Campbell PJ
影响因子：
14.9
作者：
Costello M;Pugh TJ;Fennell TJ;Stewart C;Lichtenstein L;Meldrim JC;Fostel JL;Friedrich DC;Perrin D;Dionne D;Kim S;Gabriel SB;Lander ES;Fisher S;Getz G
通讯作者：
Getz G