The significance of intertumor and intratumor heterogeneity in liver cancer

被引:165
作者
Liu, Jinping [1 ]
Dang, Hien [1 ]
Wang, Xin Wei [1 ]
机构
[1] NCI, Liver Carcinogenesis Sect, Lab Human Carcinogenesis, Ctr Canc Res, 37 Convent Dr,Bldg 37,Room 3044A, Bethesda, MD 20892 USA
关键词
HEPATOCELLULAR-CARCINOMA CELLS; EPITHELIAL-MESENCHYMAL TRANSITION; CIRCULATING TUMOR-CELLS; IN-SITU HYBRIDIZATION; SOMATIC MUTATIONS; GENETIC-HETEROGENEITY; SUPPRESSOR-CELLS; CLONAL EVOLUTION; SELF-RENEWAL; EXPRESSION;
D O I
10.1038/emm.2017.165
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Genomic analyses of primary liver cancer samples reveal a complex mutational landscape with vast intertumor and intratumor heterogeneity. Different primary liver tumors and subclones within each tumor display striking molecular and biological variations. Consequently, tumor molecular heterogeneity contributes to drug resistance and tumor relapse following therapy, which poses a substantial obstruction to improving outcomes of patients with liver cancer. There is an urgent need to the compositional and functional understanding of tumor heterogeneity. In this review, we summarize genomic and non-genomic diversities, which include stemness and microenvironmental causes of the functional heterogeneity of the primary liver cancer ecosystem. We discuss the importance and intricacy of intratumor heterogeneity in the context of cancer cell evolution. We also discuss methodologies applicable to determine intratumor heterogeneity and highlight the best-fit patient-derived in vivo and in vitro models to recapture the functional heterogeneity of primary liver cancer with the aim to improve future therapeutic strategies.
引用
收藏
页码:e416 / e416
页数:8
相关论文
共 105 条
[1]   A Message from the AACR [J].
Sawyers, Charles L. ;
Foti, Margaret .
CLINICAL CANCER RESEARCH, 2013, 19 :S6-S7
[2]   Genomic and Genetic Characterization of Cholangiocarcinoma Identifies Therapeutic Targets for Tyrosine Kinase Inhibitors [J].
Andersen, Jesper B. ;
Spee, Bart ;
Blechacz, Boris R. ;
Avital, Itzhak ;
Komuta, Mina ;
Barbour, Andrew ;
Conner, Elizabeth A. ;
Gillen, Matthew C. ;
Roskams, Tania ;
Roberts, Lewis R. ;
Factor, Valentina M. ;
Thorgeirsson, Snorri S. .
GASTROENTEROLOGY, 2012, 142 (04) :1021-U552
[3]   Fully Automated RNAscope In Situ Hybridization Assays for Formalin-Fixed Paraffin-Embedded Cells and Tissues [J].
Anderson, Courtney M. ;
Zhang, Bingqing ;
Miller, Melanie ;
Butko, Emerald ;
Wu, Xingyong ;
Laver, Thomas ;
Kernag, Casey ;
Kim, Jeffrey ;
Luo, Yuling ;
Lamparski, Henry ;
Park, Emily ;
Su, Nan ;
Ma, Xiao-Jun .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2016, 117 (10) :2201-2208
[4]  
[Anonymous], HEPATIC ONCOLOGY
[5]   SELECTIVE G-MUTATION TO T-MUTATION OF P53 GENE IN HEPATOCELLULAR-CARCINOMA FROM SOUTHERN AFRICA [J].
BRESSAC, B ;
KEW, M ;
WANDS, J ;
OZTURK, M .
NATURE, 1991, 350 (6317) :429-431
[6]   A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to Screen Anticancer Compounds [J].
Bruna, Alejandra ;
Rueda, Oscar M. ;
Greenwood, Wendy ;
Batra, Ankita Sati ;
Callari, Maurizio ;
Batra, Rajbir Nath ;
Pogrebniak, Katherine ;
Sandoval, Jose ;
Cassidy, John W. ;
Tufegdzic-Vidakovic, Ana ;
Sammut, Stephen-John ;
Jones, Linda ;
Provenzano, Elena ;
Baird, Richard ;
Eirew, Peter ;
Hadfield, James ;
Eldridge, Matthew ;
McLaren-Douglas, Anne ;
Barthorpe, Andrew ;
Lightfoot, Howard ;
O'Connor, Mark J. ;
Gray, Joe ;
Cortes, Javier ;
Baselga, Jose ;
Marangoni, Elisabetta ;
Welm, Alana L. ;
Aparicio, Samuel ;
Serra, Violeta ;
Garnett, Mathew J. ;
Caldas, Carlos .
CELL, 2016, 167 (01) :260-+
[7]   Tissue microarray (TMA) technology:: miniaturized pathology archives for high-throughput in situ studies [J].
Bubendorf, L ;
Nocito, A ;
Moch, H ;
Sauter, G .
JOURNAL OF PATHOLOGY, 2001, 195 (01) :72-79
[8]   Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment [J].
Budhu, Anuradha ;
Forgues, Marshonna ;
Ye, Qing-Hai ;
Jia, Hu-Liong ;
He, Ping ;
Zanetti, Krista A. ;
Kammula, Udai S. ;
Chen, Yidong ;
Qin, Lun-Xiu ;
Tang, Zhao-You ;
Wang, Xin Wei .
CANCER CELL, 2006, 10 (02) :99-111
[9]   Wnt signalling modulates transcribed-ultraconserved regions in hepatobiliary cancers [J].
Carotenuto, Pietro ;
Fassan, Matteo ;
Pandolfo, Rosantony ;
Lampis, Andrea ;
Vicentini, Caterina ;
Cascione, Luciano ;
Paulus-Hock, Viola ;
Boulter, Luke ;
Guest, Rachel ;
Quagliata, Luca ;
Hahne, Jens Claus ;
Ridgway, Rachel ;
Jamieson, Tam ;
Athineos, Dimitris ;
Veronese, Angelo ;
Visone, Rosa ;
Murgia, Claudio ;
Ferrari, Giulia ;
Guzzardo, Vincenza ;
Evans, Thomas Ronald Jeffry ;
MacLeod, Martin ;
Feng, Gui Ji ;
Dale, Trevor ;
Negrini, Massimo ;
Forbes, Stuart J. ;
Terracciano, Luigi ;
Scarpa, Aldo ;
Patel, Tushar ;
Valeri, Nicola ;
Workman, Paul ;
Sansom, Owen ;
Braconi, Chiara .
GUT, 2017, 66 (07) :1268-1277
[10]   Spatially resolved, highly multiplexed RNA profiling in single cells [J].
Chen, Kok Hao ;
Boettiger, Alistair N. ;
Moffitt, Jeffrey R. ;
Wang, Siyuan ;
Zhuang, Xiaowei .
SCIENCE, 2015, 348 (6233)