The spatial organization of intra-tumour heterogeneity and evolutionary trajectories of metastases in hepatocellular carcinoma
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 diversif...
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sg-ntu-dr.10356-896072023-02-28T17:03:10Z The spatial organization of intra-tumour heterogeneity and evolutionary trajectories of metastases in hepatocellular carcinoma 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 School of Biological Sciences Copy Number Variation Cancer Genomics 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. NMRC (Natl Medical Research Council, S’pore) Published version 2018-06-07T07:01:02Z 2019-12-06T17:29:26Z 2018-06-07T07:01:02Z 2019-12-06T17:29:26Z 2017 Journal Article 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-. https://hdl.handle.net/10356/89607 http://hdl.handle.net/10220/44986 10.1038/ncomms14565 en Nature Communications © 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/ 9 p. application/pdf |
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Copy Number Variation Cancer Genomics 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 The spatial organization of intra-tumour heterogeneity and evolutionary trajectories of metastases in hepatocellular carcinoma |
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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. |
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School of Biological Sciences |
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School of Biological Sciences 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 |
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Article |
author |
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 |
author_sort |
Zhai, Weiwei |
title |
The spatial organization of intra-tumour heterogeneity and evolutionary trajectories of metastases in hepatocellular carcinoma |
title_short |
The spatial organization of intra-tumour heterogeneity and evolutionary trajectories of metastases in hepatocellular carcinoma |
title_full |
The spatial organization of intra-tumour heterogeneity and evolutionary trajectories of metastases in hepatocellular carcinoma |
title_fullStr |
The spatial organization of intra-tumour heterogeneity and evolutionary trajectories of metastases in hepatocellular carcinoma |
title_full_unstemmed |
The spatial organization of intra-tumour heterogeneity and evolutionary trajectories of metastases in hepatocellular carcinoma |
title_sort |
spatial organization of intra-tumour heterogeneity and evolutionary trajectories of metastases in hepatocellular carcinoma |
publishDate |
2018 |
url |
https://hdl.handle.net/10356/89607 http://hdl.handle.net/10220/44986 |
_version_ |
1759855675927691264 |