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https://hdl.handle.net/10356/89607
Title: | The spatial organization of intra-tumour heterogeneity and evolutionary trajectories of metastases in hepatocellular carcinoma | Authors: | Zhai, Weiwei Choo, Su-Pin Khor, Chiea Chuen Lim, Tony Kiat-Hon Zhang, Tong Phang, Su-Ting Tiang, Zenia Guan, Peiyong Ng, Ming-Hwee Lim, Jia Qi Yao, Fei Li, Zheng Ng, Poh Yong Yan, Jie Goh, Brian K. Chung, Alexander Yaw-Fui Soon, Wendy Wei-Jia Sung, Ken Wing-Kin Foo, Roger Sik-Yin Chow, Pierce Kah-Hoe |
Keywords: | Copy Number Variation Cancer Genomics |
Issue Date: | 2017 | Source: | Zhai, W., Lim, T. K.-H., Zhang, T., Phang, S.-T., Tiang, Z., Guan, P., et al. (2017). The spatial organization of intra-tumour heterogeneity and evolutionary trajectories of metastases in hepatocellular carcinoma. Nature Communications, 8, 4565-. | Series/Report no.: | Nature Communications | Abstract: | 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. | URI: | https://hdl.handle.net/10356/89607 http://hdl.handle.net/10220/44986 |
DOI: | 10.1038/ncomms14565 | Rights: | © 2017 The Author(s). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ | Fulltext Permission: | open | Fulltext Availability: | With Fulltext |
Appears in Collections: | SBS Journal Articles |
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