Unraveling the chaotic genomic landscape of primary and metastatic canine appendicular osteosarcoma with current sequencing technologies and bioinformatic approaches.
Unraveling the chaotic genomic landscape of primary and metastatic canine appendicular osteosarcoma with current sequencing technologies and bioinformatic approaches.
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DOI：
10.1371/journal.pone.0246443
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Bryan JN
中科院分区：
文献类型：
--
作者：
Chu S;Skidmore ZL;Kunisaki J;Walker JR;Griffith M;Griffith OL;Bryan JN
骨肉瘤在儿童中是一种罕见的疾病，但在成年大型犬中是最常见的癌症之一。使用自动化全基因组测序、外显子组和RNA-seq管道（适用于本研究，用于犬），全面评估了两只患有非骨肉瘤（OSA）的犬的原发性和肺转移性肿瘤的突变情况。染色体病变是最常见的突变类型。犬之间的突变景观差异很大，但同一患者的病变相似。突变体TP 53中的拷贝数中性杂合性丢失是最显著的驱动突变，并且涉及5号染色体中部的大区域。犬和人类阻塞性睡眠呼吸暂停的特征是细胞周期检查点完整性和DNA损伤反应途径的丧失。考虑到我们的研究和以前的研究中观察到的异质性，建议在靶向治疗之前对患有犬OSA的个体患者进行突变谱分析。
Osteosarcoma is a rare disease in children but is one of the most common cancers in adult large breed dogs. The mutational landscape of both the primary and pulmonary metastatic tumor in two dogs with appendicular osteosarcoma (OSA) was comprehensively evaluated using an automated whole genome sequencing, exome and RNA-seq pipeline that was adapted for this study for use in dogs. Chromosomal lesions were the most common type of mutation. The mutational landscape varied substantially between dogs but the lesions within the same patient were similar. Copy number neutral loss of heterozygosity in mutant TP53 was the most significant driver mutation and involved a large region in the middle of chromosome 5. Canine and human OSA is characterized by loss of cell cycle checkpoint integrity and DNA damage response pathways. Mutational profiling of individual patients with canine OSA would be recommended prior to targeted therapy, given the heterogeneity seen in our study and previous studies.
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影响因子：
19
作者：
Bendris N;Schmid SL
通讯作者：
Schmid SL
影响因子：
6.4
作者：
Al-Hebshi NN;Li S;Nasher AT;El-Setouhy M;Alsanosi R;Blancato J;Loffredo C
通讯作者：
Loffredo C
影响因子：
3.5
作者：
Haase M;Fitze G
通讯作者：
Fitze G
端粒：一种倍性 - 敏锐的方法，用于从整个基因组测序数据中估算端粒长度。
影响因子：
4.6
作者：
Farmery JHR;Smith ML;NIHR BioResource - Rare Diseases;Lynch AG
通讯作者：
Lynch AG
31种癌症类型的端粒长度和躯体改变的系统分析。
影响因子：
30.8
作者：
Barthel FP;Wei W;Tang M;Martinez-Ledesma E;Hu X;Amin SB;Akdemir KC;Seth S;Song X;Wang Q;Lichtenberg T;Hu J;Zhang J;Zheng S;Verhaak RG
通讯作者：
Verhaak RG