DNA repair pathway profiling and microsatellite instability in colorectal cancer
| Autor: | Paul J. Goodfellow, Mary Ann Mallon, Wanghai Zhang, Robert R. Freimuth, Sharon Marsh, Howard L. McLeod, Mark A. Watson, Jinsheng Yu |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Adult
Male Cancer Research DNA Repair DNA repair Apoptosis DNA-Directed DNA Polymerase Biology MLH1 XRCC1 medicine Humans RNA Messenger HMGB1 Protein Poly-ADP-Ribose Binding Proteins Adaptor Proteins Signal Transducing Aged Genetics Aged 80 and over Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling DNA Helicases Microsatellite instability Nuclear Proteins DNA Repair Pathway DNA Neoplasm DNA Methylation Middle Aged medicine.disease DNA-Binding Proteins Real-time polymerase chain reaction DNA Repair Enzymes MutS Homolog 2 Protein X-ray Repair Cross Complementing Protein 1 Oncology MSH2 DNA methylation Cancer research Female Microsatellite Instability Colorectal Neoplasms MutL Protein Homolog 1 |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 12(17) |
| ISSN: | 1078-0432 |
| Popis: | Background: The ability to maintain DNA integrity is a critical cellular function. DNA repair is conducted by distinct pathways of genes, many of which are thought to be altered in colorectal cancer. However, there has been little characterization of these pathways in colorectal cancer. Method: By using the TaqMan real-time quantitative PCR, RNA expression profiling of 20 DNA repair pathway genes was done in matched tumor and normal tissues from 52 patients with Dukes' C colorectal cancer. Results: The relative mRNA expression level across the 20 DNA repair pathway genes varied considerably, and the individual variability was also quite large, with an 85.4 median fold change in the tumor tissue genes and a 127.2 median fold change in the normal tissue genes. Tumor-normal differential expression was found in 13 of 20 DNA repair pathway genes (only XPA had a lower RNA level in the tumor samples; the other 12 genes had significantly higher tumor levels, all P < 0.01). Coordinated expression of ERCC6, HMG1, MSH2, and POLB (RS ≥ 0.60) was observed in the tumor tissues (all P < 0.001). Apoptosis index was not correlated with expression of the 20 DNA repair pathway genes. MLH1 and XRCC1 RNA expression was correlated with microsatellite instability status (P = 0.045 and 0.020, respectively). An inverse correlation was found between tumor MLH1 RNA expression and MLH1 DNA methylation (P = 0.003). Conclusion: Our study provides an initial characterization of the DNA repair pathways for understanding the cellular DNA damage/repair system in human colorectal cancer. |
| Databáze: | OpenAIRE |
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