Targets of genome copy number reduction in primary breast cancers identified by integrative genomics
| Autor: | Kosei Ito, Andrew G Tay, Bien-Keem Tan, Kok Chai Tan, Benita Tan, Patrick Tan, Manuel Salto-Tellez, Wei Chen, L.K. Tan, Nallasivam Palanisamy, Yoshiaki Ito, Puay Hoon Tan, Erik S. W. Ang, Lang Hiong Sii, Kumaresan Ganesan, Qingsong Hou, Jeanie Wu |
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| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
Candidate gene Gene Dosage Down-Regulation Breast Neoplasms Genomics Biology Bioinformatics Polymorphism Single Nucleotide Gene dosage Genome Breast cancer Cell Line Tumor Genetics medicine Humans Genes Tumor Suppressor Neoplasm Invasiveness RNA Messenger RNA Neoplasm Gene Oligonucleotide Array Sequence Analysis Tissue microarray Genome Human Gene Expression Profiling medicine.disease Gene expression profiling Core Binding Factor Alpha 3 Subunit Cancer research Female Genes Neoplasm |
| Zdroj: | Genes, Chromosomes and Cancer. 46:288-301 |
| ISSN: | 1098-2264 1045-2257 |
| DOI: | 10.1002/gcc.20411 |
| Popis: | The identification of specific oncogenes and tumor suppressor genes in regions of recurrent aneuploidy is a major challenge of molecular cancer research. Using both oligonucleotide single-nucleotide polymorphism and mRNA expression arrays, we integrated genomic and transcriptional information to identify and prioritize candidate cancer genes in regions of increased and decreased chromosomal copy number in a cohort of primary breast cancers. Confirming the validity of this approach, several regions of previously-known copy number (CN) alterations in breast cancer could be successfully reidentified. Focusing on regions of decreased CN, we defined a prioritized list of eighteen candidate genes, which included ARPIN, FBN1, and LZTS1, previously shown to be associated with cancers in breast or other tissue types, and novel genes such as P29, MORF4L1, and TBC1D5. One such gene, the RUNX3 transcription factor, was selected for further study. We show that RUNX3 is present at reduced CNs in proportion to the rest of the tumor genome and that RUNX3 CN reductions can also be observed in a breast cancer series from a different center. Using tissue microarrays, we demonstrate in an independent cohort of over 120 breast tissues that RUNX3 protein is expressed in normal breast epithelium but not fat and stromal tissue, and widely down-regulated in the majority of breast cancers (>85%). In vitro, RUNX3 overexpression suppressed the invasive potential of MDA-MB-231 breast cancer cells in a matrigel assay. Our results demonstrate the utility of integrative genomic approaches to identify novel potential cancer-related genes in primary tumors. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat. |
| Databáze: | OpenAIRE |
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