The spatial organization of intra-tumour heterogeneity and evolutionary trajectories of metastases in hepatocellular carcinoma

Weiwei Zhai (), Tony Kiat-Hon Lim, Tong Zhang, Su-Ting Phang, Zenia Tiang, Peiyong Guan, Ming-Hwee Ng, Jia Qi Lim, Fei Yao, Zheng Li, Poh Yong Ng, Jie Yan, Brian K. Goh, Alexander Yaw-Fui Chung, Su-Pin Choo, Chiea Chuen Khor, Wendy Wei-Jia Soon, Ken Wing-Kin Sung, Roger Sik-Yin Foo () and Pierce Kah-Hoe Chow ()
Additional contact information
Weiwei Zhai: Genome Institute of Singapore, Agency for Science, Technology and Research
Tony Kiat-Hon Lim: Singapore General Hospital
Tong Zhang: Genome Institute of Singapore, Agency for Science, Technology and Research
Su-Ting Phang: National Cancer Centre
Zenia Tiang: Genome Institute of Singapore, Agency for Science, Technology and Research
Peiyong Guan: Genome Institute of Singapore, Agency for Science, Technology and Research
Ming-Hwee Ng: Genome Institute of Singapore, Agency for Science, Technology and Research
Jia Qi Lim: Genome Institute of Singapore, Agency for Science, Technology and Research
Fei Yao: Genome Institute of Singapore, Agency for Science, Technology and Research
Zheng Li: Genome Institute of Singapore, Agency for Science, Technology and Research
Poh Yong Ng: Genome Institute of Singapore, Agency for Science, Technology and Research
Jie Yan: Genome Institute of Singapore, Agency for Science, Technology and Research
Brian K. Goh: Singapore General Hospital
Alexander Yaw-Fui Chung: Singapore General Hospital
Su-Pin Choo: National Cancer Centre
Chiea Chuen Khor: Genome Institute of Singapore, Agency for Science, Technology and Research
Wendy Wei-Jia Soon: Genome Institute of Singapore, Agency for Science, Technology and Research
Ken Wing-Kin Sung: Genome Institute of Singapore, Agency for Science, Technology and Research
Roger Sik-Yin Foo: Genome Institute of Singapore, Agency for Science, Technology and Research
Pierce Kah-Hoe Chow: National Cancer Centre

Nature Communications, 2017, vol. 8, issue 1, 1-9

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms14565

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