Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer.
Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer.
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DOI：
10.1038/ng.3764
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发表时间：
2017-03
期刊：
影响因子：
30.8
通讯作者：
Iacobuzio-Donahue CA
中科院分区：
文献类型：
--
作者：
Makohon-Moore AP;Zhang M;Reiter JG;Bozic I;Allen B;Kundu D;Chatterjee K;Wong F;Jiao Y;Kohutek ZA;Hong J;Attiyeh M;Javier B;Wood LD;Hruban RH;Nowak MA;Papadopoulos N;Kinzler KW;Vogelstein B;Iacobuzio-Donahue CA
在自然发生的转移性疾病中，驱动基因突变的异质性程度在很大程度上是未知的，即治疗未成熟的转移性疾病。为了解决这个问题，我们对4名患者的26个转移瘤进行了60倍全基因组测序。我们发现，在每个被研究的患者的每个转移灶中都存在相同的驱动基因突变。所有肿瘤内的异质性都是由未知或预测不具有功能性后果的乘客基因突变引起的。即使在这些客体基因突变方面，转移瘤的创始细胞之间的遗传相似性也明显高于从正常组织中随机抽取的任何两个细胞的遗传相似性。在同一患者的转移中，驱动基因突变的一致性对于未来晚期疾病靶向治疗的成功具有关键的、令人鼓舞的影响。
The extent of heterogeneity of driver gene mutations present in naturally occurring metastases is largely unknown, i.e. treatment-naïve metastatic disease. To address this issue, 60× whole genome sequencing of 26 metastases from 4 patients was carried out. We found that the identical driver gene mutations were present in every metastatic lesion of each patient studied. Passenger gene mutations not known or predicted to have functional consequences accounted for all intratumoral heterogeneity. Even with respect to these passenger gene mutations, the genetic similarity among the founding cells of metastases was markedly higher than that expected for any two cells randomly taken from a normal tissue. The uniformity of driver gene mutations among metastases in the same patient has critical, encouraging implications for the success of future targeted therapies in advanced stage disease.
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影响因子：
64.5
作者：
Davoli T;Xu AW;Mengwasser KE;Sack LM;Yoon JC;Park PJ;Elledge SJ
通讯作者：
Elledge SJ
DOI：
10.1093/bioinformatics/btt017
发表时间：
2013-03-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Douville C;Carter H;Kim R;Niknafs N;Diekhans M;Stenson PD;Cooper DN;Ryan M;Karchin R
通讯作者：
Karchin R
影响因子：
64.8
作者：
Greaves, Mel;Maley, Carlo C.
通讯作者：
Maley, Carlo C.
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.6
作者：
Embuscado, EE;Laheru, D;Iacobuzio-Donahue, CA
通讯作者：
Iacobuzio-Donahue, CA