Hepatic Stem-like Phenotype and Interplay of Wnt/β-Catenin and Myc Signaling in Aggressive Childhood Liver Cancer

被引：387

作者：

Cairo, Stefano ^{[1
,2
]}

Armengol, Carolina ^{[1
,2
]}

De Reynies, Auelien ^{[3
]}

Wei, Yu ^{[1
,2
]}

Thomas, Emilie ^{[3
]}

Renard, Claire-Angelique ^{[1
,2
]}

Goga, Andrei ^{[4
]}

Balakrishnan, Asha ^{[4
]}

Semeraro, Michaela ^{[5
]}

Gresh, Lionel ^{[6
]}

Pontoglio, Marco ^{[6
]}

Strick-Marchand, Helene ^{[7
]}

Levillayer, Florence ^{[2
]}

Nouet, Yann ^{[2
]}

Rickman, David ^{[3
]}

Gauthier, Frederic ^{[8
]}

Branchereau, Sophie ^{[8
]}

Brugieres, Laurence ^{[9
]}

Laithier, Veronique ^{[10
]}

Bouvier, Raymonde ^{[11
]}

Boman, Francoise ^{[12
]}

Basso, Giuseppe ^{[13
]}

Michiels, Jean-Francois ^{[14
]}

Hofman, Paul ^{[15
,16
]}

Arbez-Gindre, Francine ^{[17
]}

Jouan, Helene ^{[18
]}

Chapeau, Marie-Christine Rousselet ^{[19
,20
]}

Berrebi, Dominique

Marcellin, Luc ^{[22
]}

Plenat, Francois ^{[23
]}

Zachar, Dominique ^{[21
]}

Joubert, Madeleine ^{[25
]}

Selves, Janick ^{[26
]}

Pasquier, Dominique ^{[24
,27
]}

Bioulac-Sage, Paulette ^{[28
]}

Grotzer, Michael ^{[29
]}

Childs, Margaret ^{[30
]}

Fabre, Monique ^{[31
]}

Buendia, Marie-Annick ^{[1
,2
]}

机构：

[1] Inst Pasteur, Oncogenesis & Mol Virol Unit, F-75724 Paris 15, France

[2] INSERM, U579, F-75724 Paris 15, France

[3] Programme Cartes Identite Tumeurs, F-75013 Paris, France

[4] Univ Calif San Francisco, Div Hematol Oncol, San Francisco, CA 94143 USA

[5] Inst Pasteur, Histotechnol & Pathol Unit, F-75724 Paris, France

[6] Inst Pasteur, CNRS, URA 2578, Gene Express Dev & Dis Unit, F-75724 Paris 15, France

[7] Inst Pasteur, Dept Immunol, Cytokine & Lymphoid Dev Unit, F-75724 Paris 15, France

[8] CHU Bicetre, APHP, Serv Chirurg Pediat, F-94275 Le Kremlin Bicetre, France

[9] Inst Gustave Roussy, Dept Pediat Oncol, F-94800 Villejuif, France

[10] Ctr Hosp Univ St Jacques, Pediat Hematol Oncol Serv, F-25030 Besancon, France

[11] CHU, Hop Edouard Herriot, Serv Anat & Cytol Pathol, F-69003 Lyon, France

[12] CHRU Lille, Ctr Biol Pathol, F-59000 Lille, France

[13] Univ Padua, Dept Pediat, I-35128 Padua, Italy

[14] Ctr Hosp Univ Nice, Hop Pasteur, Lab Cent Anat Pathol, F-06000 Nice, France

[15] Pasteur Hosp, Fac Med, INSERM, ERI 21, F-06000 Nice, France

[16] Pasteur Hosp, Lab Clin & Expt Pathol, F-06000 Nice, France

[17] Ctr Hosp Univ Jean Minjoz, Serv Anat & Cytol Pathol, F-25030 Besancon, France

[18] Ctr Hosp Pontchaillou, Dept Anatomopathol, F-35000 Rennes, France

[19] Univ Angers, UPRES 859, IFR 132, Lab HIFIH, F-49100 Angers, France

[20] CHU Angers, Anat Pathol Lab, F-49100 Angers, France

[21] Hop Robert Debre, F-75019 Paris, France

[22] Hop Hautepierre, Serv Anat Pathol Gen, F-67098 Strasbourg, France

[23] CHU Nancy Brabois, Dept Pathol, F-54511 Vandoeuvre Les Nancy, France

[24] Hop Maison Bianche, Lab Pol Bouin, F-51100 Reims, France

[25] CHU Nantes, F-44093 Nantes, France

[26] Hop Purpan, Lab Anat & Cytol Pathol, F-31059 Toulouse, France

[27] Ctr Hosp Univ A Michallon, Serv Anat Pathol, F-38043 Grenoble, France

[28] Univ Victor Segelan Bordeaux, INSERM, U889, CHU Bordeaux,Dept Pathol, F-33076 Bordeaux, France

[29] Univ Childrens Hosp, SIOPEL Tumor Banking Program, CH-8032 Zurich, Switzerland

[30] Univ Leicester, Childrens Canc & Leukaemia Grp Data Ctr, Leicester LE1 7RH, Leics, England

[31] Univ Paris 11, APHP Hop Bicetre, Serv Anat & Cytol Pathol, F-94275 Le Kremlin Bicetre, France

来源：

CANCER CELL | 2008年 / 14卷 / 06期

关键词：

D O I：

10.1016/j.ccr.2008.11.002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Hepatoblastoma, the most common pediatric liver cancer, is tightly linked to excessive Wnt/beta-catenin signaling. Here, we used microarray analysis to identify two tumor subclasses resembling distinct phases of liver development and a discriminating 16-gene signature. beta-catenin activated different transcriptional programs in the two tumor types, with distinctive expression of hepatic stem/progenitor markers in immature tumors. This highly proliferating subclass was typified by gains of chromosomes 8q and 2p and upregulated Myc signaling. Myc-induced hepatoblastoma-like tumors in mice strikingly resembled the human immature subtype, and Myc downregulation in hepatoblastoma cells impaired tumorigenesis in vivo. Remarkably, the 16-gene signature discriminated invasive and metastatic hepatoblastomas and predicted prognosis with high accuracy.

引用

页码：471 / 484

页数：14

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