The spatial organization of intra-tumour heterogeneity and evolutionary trajectories of metastases in hepatocellular carcinoma.
The spatial organization of intra-tumour heterogeneity and evolutionary trajectories of metastases in hepatocellular carcinoma.
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DOI：
10.1038/ncomms14565
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发表时间：
2017-02-27
影响因子：
16.6
通讯作者：
Chow PK
中科院分区：
文献类型：
--
作者：
Zhai W;Lim TK;Zhang T;Phang ST;Tiang Z;Guan P;Ng MH;Lim JQ;Yao F;Li Z;Ng PY;Yan J;Goh BK;Chung AY;Choo SP;Khor CC;Soon WW;Sung KW;Foo RS;Chow PK
肝细胞癌 (HCC) 是存活率最差的癌症之一。通过对九个具有不同病因的切除肝癌进行多区域采样，我们构建了这些部分的系统发育关系，显示出不同程度的遗传共享，涵盖早期到晚期的多样化。与结直肠癌中发现的杂色模式不同，大部分 HCC 显示出明显的距离隔离模式，其中空间上较近的部分在遗传上更加相似。两个切除的肝内转移瘤分别显示在原发性肿瘤多样化之前和之后发生的遗传分歧。转移性肿瘤比原发性肿瘤具有更高的变异性，这表明肝内转移伴随着远处位置的快速多样化。共存突变的存在为 HCC 治疗的药物重新定位提供了可能性。总而言之，这些对肿瘤内异质性的见解使我们能够全面了解 HCC 的进化轨迹，并为个性化治疗提出了新的途径。肝细胞癌是癌症中存活率最差的一种。在这里，作者强调了这种疾病的肿瘤内异质性，发现空间上更接近的肿瘤部分在遗传上更加相似，并且肝内转移伴随着快速的遗传多样化。
Hepatocellular carcinoma (HCC) has one of the poorest survival rates among cancers. Using multi-regional sampling of nine resected HCC with different aetiologies, here we construct phylogenetic relationships of these sectors, showing diverse levels of genetic sharing, spanning early to late diversification. Unlike the variegated pattern found in colorectal cancers, a large proportion of HCC display a clear isolation-by-distance pattern where spatially closer sectors are genetically more similar. Two resected intra-hepatic metastases showed genetic divergence occurring before and after primary tumour diversification, respectively. Metastatic tumours had much higher variability than their primary tumours, suggesting that intra-hepatic metastasis is accompanied by rapid diversification at the distant location. The presence of co-existing mutations offers the possibility of drug repositioning for HCC treatment. Taken together, these insights into intra-tumour heterogeneity allow for a comprehensive understanding of the evolutionary trajectories of HCC and suggest novel avenues for personalized therapy. Hepatocellular carcinoma has one of the poorest survival rates amongst cancers. Here, the authors highlight the intra-tumour heterogeneity of this disease, finding that spatially closer tumour sectors are genetically more similar and that intra-hepatic metastasis is accompanied by rapid genetic diversification.