Document Detail


Recurrent and nonrandom DNA copy number and chromosome alterations in Myc transgenic mouse model for hepatocellular carcinogenesis: implications for human disease.
MedLine Citation:
PMID:  19389504     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mouse models for hepatocellular carcinoma (HCC) provide an experimental ground for dissecting the genetic and biological complexities of human liver cancer and contribute to our ability to gain insights into the relevance of candidate cancer genes. We examined, using spectral karyotyping (SKY) and array-based CGH (aCGH), seven cell lines derived from HCC spontaneously developed in transgenic Myc mice (Myc), and four cell lines established from tumors induced in nude mice by inoculation with the original Myc cells (nuMyc). All the cell lines exhibited gain of material from chromosomes 5, 6, 8, 10, 11, 15, and 19 and DNA copy-number loss from chromosomes 2, 4, 7, 9, 12, 14, and X. In addition, several recurrent chromosome reorganizations were found, including del(3), t(3;8), del(4), t(4;11), t(6;5), del(7), del(8), del(9), t(10;14), del(11), and del(16). Chromosome breakpoints underlying rearrangements clustered in the regions previously identified as important for the early stages of Myc-induced hepatocarcinogenesis. The results strongly suggest the importance of recurrent breakage and loss of chromosomes 4, 9, and 14 and gain of chromosomes 15 and 19 in mouse liver neoplasia. Genomic changes observed in Myc HCC cell lines are also recurrent in HCC developed in other transgenic mouse models, in mouse spontaneous HCC and derivative cell lines, and in preneoplastic liver lesions induced with chemical carcinogens. Overall, the present results document selective, nonrandom genomic changes involving chromosomal regions homologous to those implicated in human HCC.
Authors:
Drazen B Zimonjic; Veronika Ullmannova-Benson; Valentina M Factor; Snorri S Thorgeirsson; Nicholas C Popescu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural    
Journal Detail:
Title:  Cancer genetics and cytogenetics     Volume:  191     ISSN:  1873-4456     ISO Abbreviation:  Cancer Genet. Cytogenet.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-04-24     Completed Date:  2009-05-05     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  7909240     Medline TA:  Cancer Genet Cytogenet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17-26     Citation Subset:  IM    
Affiliation:
Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, 37 Convent Drive MSC 4262, Building 37, Room 4128B, Bethesda, MD 20892, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Carcinoma, Hepatocellular / genetics*,  pathology
Cell Line, Tumor
Chromosome Aberrations*
Chromosomes, Mammalian / genetics
Comparative Genomic Hybridization
DNA, Neoplasm / genetics*
Disease Models, Animal
Gene Dosage*
Gene Rearrangement
Humans
Injections, Subcutaneous
Liver Neoplasms / genetics*,  pathology
Mice
Mice, Transgenic
Proto-Oncogene Proteins c-myc / genetics*,  metabolism*
Spectral Karyotyping
Grant Support
ID/Acronym/Agency:
Z01 BC010038-12/BC/NCI NIH HHS; Z99 CA999999/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/DNA, Neoplasm; 0/Proto-Oncogene Proteins c-myc
Comments/Corrections

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