Please use this identifier to cite or link to this item: https://doi.org/10.1038/ncomms14565
Title: The spatial organization of intra-tumour heterogeneity and evolutionary trajectories of metastases in hepatocellular carcinoma
Authors: Zhai, W
Lim, T.K.-H 
Zhang, T
Phang, S.-T
Tiang, Z 
Guan, P
Ng, M.-H
Lim, J.Q
Yao, F
Li, Z
Ng, P.Y
Yan, J 
Goh, B.K 
Chung, A.Y.-F 
Choo, S.-P 
Khor, C.C 
Soon, W.W.-J
Sung, K.W.-K 
Foo, R.S.-Y 
Chow, P.K.-H 
Keywords: cancer
etiology
genetic variation
heterogeneity
homeostasis
mutation
tumor
Article
controlled study
copy number variation
disease course
drug repositioning
gene mutation
genetic variability
human
human tissue
liver cell carcinoma
liver metastasis
metastasis
phenotype
phylogeny
primary tumor
biopsy
DNA sequence
genetics
human genome
liver
liver cell carcinoma
liver tumor
metastasis
mutation
pathology
virology
virus DNA cell DNA interaction
Biopsy
Carcinoma, Hepatocellular
DNA Copy Number Variations
Genome, Human
Humans
Liver
Liver Neoplasms
Mutation
Neoplasm Metastasis
Phenotype
Phylogeny
Sequence Analysis, DNA
Virus Integration
Issue Date: 2017
Publisher: Nature Publishing Group
Citation: Zhai, W, Lim, T.K.-H, Zhang, T, Phang, S.-T, Tiang, Z, Guan, P, Ng, M.-H, Lim, J.Q, Yao, F, Li, Z, Ng, P.Y, Yan, J, Goh, B.K, Chung, A.Y.-F, Choo, S.-P, Khor, C.C, Soon, W.W.-J, Sung, K.W.-K, Foo, R.S.-Y, Chow, P.K.-H (2017). The spatial organization of intra-tumour heterogeneity and evolutionary trajectories of metastases in hepatocellular carcinoma. Nature Communications 8 : 4565. ScholarBank@NUS Repository. https://doi.org/10.1038/ncomms14565
Rights: Attribution 4.0 International
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. © 2017 Japan Antibiotics Research Association All rights reserved.
Source Title: Nature Communications
URI: https://scholarbank.nus.edu.sg/handle/10635/179733
ISSN: 2041-1723
DOI: 10.1038/ncomms14565
Rights: Attribution 4.0 International
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