Page 72 - ebook HCC

70 PROGRAMME AND ABSTRACTS GENEVA, SWITZERLAND EASL HCC SUMMIT 71
FEBRUARY 13 - 16, 2014

SPECIFIC GENOMIC AND TRANSCRIPTOMIC
ABERRATIONS IN HCC INDUCED BY PARTIAL
HEPATECTOMY OF A CHRONICALLY INFLAMED
LIVER

Ezra Ella , Evgeniy Stoyanov , Orit Pappo , Denise Heim , Temima Schnitzer Perlman , Amplifications in spontaneous tumors affected fewer chromosomes and were not located
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Nathalie Nachmansson , Rona Steinfeld , Israel Steinfeld , Ludmila Rivkin , Deborah preferentially at chromosomal edges. PHx-induced and spontaneous tumors shared
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Olam , Henning Wege , Rinat Abramovitch , Eithan Galun , Daniel Goldenberg 1 the same frequently amplified region at chromosome 18. One of the regulatory genes
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1 Goldyne Savad Institute of Gene Therapy, Department of Pathology, Hadassah- encoded by this amplified region, Crem, was up-regulated in many published human
Hebrew University Medical Center, Jerusalem, Israel, Department of Gastroenterology HCC datasets. Here, we demonstrated its nuclear expression in human HCC, and its
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and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, pro-proliferative activity in human HCC cell lines in vitro. Comparison of gene expression
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4 Computer Science Department, Technion-Israel Institute of Technology, Haifa, Magnetic profiles revealed very limited numbers of common up- and down-regulated genes in the
Resonance Imaging/Magnetic Resonance Spectroscopy Laboratory, Hadassah-Hebrew post-PHx and spontaneous tumors. Post-PHx tumors were significantly enriched with
expression signatures of oncogenes, chromosomal instability markers and E2F1 targets.
BASIC SPEAKERS ABSTRACTS Introduction: The Mdr2-KO mouse is a model for inflammation-mediated hepatocellular prognosis” HCC-specific gene expression signatures. BASIC SPEAKERS ABSTRACTS
University Medical Center, Jerusalem, Israel
Both tumors and non-tumor liver tissues of the post-PHx mice were enriched with the “poor
Corresponding author’s e-mail: goldenberg@hadassah.org.il
Conclusions: PHx of the chronically inflamed liver directed tumor development to a
discrete pathway characterized by amplification of specific chromosomal regions and
expression of specific tumor-promoting genes. Liver PHx in Mdr2-KO mice may serve
carcinoma (HCC). Previously, we demonstrated that partial hepatectomy (PHx) promotes
as a model for HCC recurrence in patients. Crem is a candidate oncogene frequently
hepatocarcinogenesis in this model (PNAS 2010, 107:2207-12).
Aims: To explore the molecular mechanisms underlying the tumor-promoting effect of amplified in this model.
PHx, we compared genomic and transcriptomic profiles of the HCC tumors induced by
70% PHx with spontaneous tumors developing in the Mdr2-KO mice.
Methodology: Six tumors from each experimental group were compared with their
matched non-tumorous liver tissue samples using microarray-based comparative genomic
hybridization and genome-scale gene expression profiling. HCC tumors subjected to
genomic analysis in both groups were similar in size and morphology.
Results: In hepatectomized mice, HCC developed three months earlier than in untreated
mice. Among PHx-induced tumors, 5/6 had major chromosomal aberrations: all of them
were amplifications affecting multiple chromosomes, and most of them were located near
the acrocentric centromeres. Four different chromosomal regions were amplified each
in at least four tumors. All six tumors of untreated mice had chromosomal aberrations,
including both deletions and amplifications.