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High-resolution gene copy number and expression profiling of human chromosome 22 in ovarian carcinomas

Benetkiewicz, M., Wang, Y., Schaner, M., Wang, P., Mantripragada, Kiran Kumar, Buckley, P. G., Kristensen, G., Borresen-Dale, A. L. and Dumanski, J. P. 2005. High-resolution gene copy number and expression profiling of human chromosome 22 in ovarian carcinomas. Genes, Chromosomes and Cancer 42 (3) , pp. 228-237. 10.1002/gcc.20128

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Abstract

Previous low-resolution studies of chromosome 22 in ovarian carcinoma have suggested its involvement in the development of the disease. We report a high-resolution analysis of DNA copy number and gene expression of 22q in 18 ovarian carcinomas using a 22q-specific genomic microarray. We identified aberrations in 67% of the studied tumors, which displayed 3 distinct gene copy number profiles. The majority of the cases (11 of 18) demonstrated heterozygous terminal deletions of various sizes, the smallest of which was 3.5 Mb. The second profile, detected in 3 tumors, revealed the coexistence of heterozygous deletions and different patterns of low-copy-number gain that involved the proximal half of 22q. The latter finding has not been reported previously in ovarian carcinoma. One case displayed a continuous deletion encompassing the entire 22q, consistent with monosomy 22. Furthermore, we compared the results with the available data on these tumors by using cDNA microarrays to define the degree of correlation between abnormalities at the DNA level and variation in mRNA expression. By a comparison with the expression data, we were able to identify 21 deleted genes showing low mRNA levels and 12 amplified genes displaying elevated gene expression, several of which play roles in cell cycle control and the induction of apoptosis. Our results indicated significant correlation between DNA copy number aberrations and variation in mRNA expression. We also identified several regions and candidate genes on 22q that should be studied further to determine their role in the development of ovarian cancer.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: R Medicine > R Medicine (General)
Publisher: Wiley-Liss Inc
ISSN: 1045-2257
Last Modified: 04 Jun 2017 08:43
URI: http://orca-mwe.cf.ac.uk/id/eprint/83565

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