Distant metastasis occurs late during the genetic evolution of pancreatic cancer.
Distant metastasis occurs late during the genetic evolution of pancreatic cancer.
复制标题
DOI：
10.1038/nature09515
复制
发表时间：
2010-10-28
期刊：
影响因子：
64.8
通讯作者：
Iacobuzio-Donahue CA
中科院分区：
文献类型：
--
作者：
Yachida S;Jones S;Bozic I;Antal T;Leary R;Fu B;Kamiyama M;Hruban RH;Eshleman JR;Nowak MA;Velculescu VE;Kinzler KW;Vogelstein B;Iacobuzio-Donahue CA
转移，即肿瘤细胞在不同于其起源器官的器官中传播和生长，是癌症患者最常见的死亡原因。对于胰腺癌来说尤其如此，大多数患者被诊断患有转移性疾病，很少有人对化疗或放疗表现出持续的反应。与其他类型癌症患者相比，胰腺癌患者的预后较差是否是由于诊断较晚或疾病早期传播到远处器官所致尚不清楚。在这里，我们依靠对七种胰腺癌转移的基因组进行测序所生成的数据来评估原发性癌症和转移性癌症之间的克隆关系。我们发现引起远处转移的克隆群体在原发癌中有所代表，但这些克隆是从原始亲本非转移性克隆遗传进化而来的。因此，转移瘤的遗传异质性反映了原发癌内的遗传异质性。对胰腺癌遗传进化的时间进行了定量分析，表明起始突变的发生和亲本非转移创始细胞的诞生之间至少有十年的时间。获得转移能力至少还需要五年，患者平均在两年后死亡。这些数据为胰腺癌进展的遗传特征提供了新的见解，并定义了早期检测以防止转移性疾病死亡的广泛时间窗口。
Metastasis, the dissemination and growth of neoplastic cells in an organ distinct from that in which they originated , is the most common cause of death in cancer patients. This is particularly true for pancreatic cancers, where most patients are diagnosed with metastatic disease and few show a sustained response to chemo- or radiation therapy . Whether the dismal prognosis of patients with pancreatic cancer compared to patients with other types of cancer is a result of late diagnosis or early dissemination of disease to distant organs is not known. Here we rely on data generated by sequencing the genomes of seven pancreatic cancer metastases to evaluate the clonal relationships among primary and metastatic cancers. We find that clonal populations that give rise to distant metastases are represented within the primary carcinoma, but these clones are genetically evolved from the original parental, non-metastatic clone. Thus, genetic heterogeneity of metastases reflects that within the primary carcinoma. A quantitative analysis of the timing of the genetic evolution of pancreatic cancer was performed, indicating at least a decade between the occurrence of the initiating mutation and the birth of the parental, non-metastatic founder cell. At least five more years are required for the acquisition of metastatic ability and patients die an average of two years thereafter. These data provide novel insights into the genetic features underlying pancreatic cancer progression and define a broad time window of opportunity for early detection to prevent deaths from metastatic disease.
登录
查看更多内容
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
DOI：
10.1073/pnas.0712345105
发表时间：
2008-03-18
影响因子：
11.1
作者：
Jones, Sian;Chen, Wei-dong;Markowitz, Sanford D.
通讯作者：
Markowitz, Sanford D.
DOI：
10.1126/science.1171362
发表时间：
2009-06-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Olive KP;Jacobetz MA;Davidson CJ;Gopinathan A;McIntyre D;Honess D;Madhu B;Goldgraben MA;Caldwell ME;Allard D;Frese KK;Denicola G;Feig C;Combs C;Winter SP;Ireland-Zecchini H;Reichelt S;Howat WJ;Chang A;Dhara M;Wang L;Rückert F;Grützmann R;Pilarsky C;Izeradjene K;Hingorani SR;Huang P;Davies SE;Plunkett W;Egorin M;Hruban RH;Whitebread N;McGovern K;Adams J;Iacobuzio-Donahue C;Griffiths J;Tuveson DA
通讯作者：
Tuveson DA
影响因子：
4.3
作者：
Hisa, Takeshi;Ohkubo, Hiroki;Suda, Koichi
通讯作者：
Suda, Koichi