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Genomic Evolution of Breast Cancer Metastasis and Relapse.
Cancer Cell ( IF 50.3 ) Pub Date : 2017-08-14 , DOI: 10.1016/j.ccell.2017.07.005
Lucy R Yates 1 , Stian Knappskog 2 , David Wedge 3 , James H R Farmery 4 , Santiago Gonzalez 5 , Inigo Martincorena 6 , Ludmil B Alexandrov 7 , Peter Van Loo 8 , Hans Kristian Haugland 9 , Peer Kaare Lilleng 9 , Gunes Gundem 10 , Moritz Gerstung 5 , Elli Pappaemmanuil 10 , Patrycja Gazinska 11 , Shriram G Bhosle 6 , David Jones 6 , Keiran Raine 6 , Laura Mudie 6 , Calli Latimer 6 , Elinor Sawyer 12 , Christine Desmedt 13 , Christos Sotiriou 13 , Michael R Stratton 6 , Anieta M Sieuwerts 14 , Andy G Lynch 4 , John W Martens 14 , Andrea L Richardson 15 , Andrew Tutt 16 , Per Eystein Lønning 2 , Peter J Campbell 6
Affiliation  

Patterns of genomic evolution between primary and metastatic breast cancer have not been studied in large numbers, despite patients with metastatic breast cancer having dismal survival. We sequenced whole genomes or a panel of 365 genes on 299 samples from 170 patients with locally relapsed or metastatic breast cancer. Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor. Most distant metastases acquired driver mutations not seen in the primary tumor, drawing from a wider repertoire of cancer genes than early drivers. These include a number of clinically actionable alterations and mutations inactivating SWI-SNF and JAK2-STAT3 pathways.

中文翻译:

乳腺癌转移和复发的基因组进化。

尽管转移性乳腺癌患者的生存率很低,但尚未对原发性和转移性乳腺癌之间的基因组进化模式进行大量研究。我们对来自 170 名局部复发或转移性乳腺癌患者的 299 个样本的全基因组或一组 365 个基因进行了测序。几条分析表明,播种转移或复发的克隆从原发性肿瘤传播较晚,但继续获得突变,主要是访问在原发性肿瘤中活跃的相同突变过程。大多数远处转移获得了在原发性肿瘤中未见的驱动突变,与早期驱动相比,它来自更广泛的癌症基因库。这些包括许多临床上可操作的改变和突变,使 SWI-SNF 和 JAK2-STAT3 通路失活。
更新日期:2017-08-14
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