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DNA copy number changes associated with characteristic LOH in islet cell carcinomas of transgenic mice
Author(s) -
Shi Yu Ping,
Naik Paul,
Dietrich William F.,
Gray Joe W.,
Hanahan Douglas,
Pinkel Daniel
Publication year - 1997
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/(sici)1098-2264(199706)19:2<104::aid-gcc6>3.0.co;2-2
Subject(s) - biology , loss of heterozygosity , comparative genomic hybridization , copy number variation , gene dosage , gene , copy number analysis , microbiology and biotechnology , genome , gene duplication , genetics , cancer research , gene expression , allele
Comparative genomic hybridization (CGH) provides a method of surveying the entire tumor genome for regional variations in DNA sequence copy number. Such variations, if found recurrently, may indicate the locations of genes that contribute to tumor development through upregulation of oncogenes (copy number increase), inactivation of tumor‐suppressor genes (copy number decrease), or changes in the level of expression through gene dosage effects. Thus, CGH is a powerful tool for screening for new cancer genes. Although CGH is widely applied to human genome analysis, application to the mouse is only beginning. The present study is designed to compare results obtained by CGH with those obtained by other techniques used for analysis of the murine genome. We report CGH analysis of several control cell lines with cytogenetically established regional copy number changes, as well as analysis of 16 primary insulinomas, four tumor‐derived cell lines, and three hyperplasia‐derived cell lines from transgenic mice expressing the SV40 large T antigen under control of the rat insulin promoter. Loss of heterozygosity (LOH) on chromosomes 9 and 16 had previously been found to be frequent in primary insulinomas, and specimens were selected for the present study based on the LOH status of these chromosomes. We found complete concordance of the CGH results with the cytogenetically described copy number changes in the control cell lines and with the LOH on chromosomes 9 and 16 in the tumors. Thus, CGH can provide accurate data in murine systems, and it reveals that the LOH in these islet cell tumors most frequently results from deletion of one of the alleles. Genes Chromosom. Cancer 19:104–111, 1997. © 1997 Wiley‐Liss, Inc.