Studies from Mayo Clinic have provided new data on colon cancer
2007 NOV 19 -- Data detailed in 'Mutations in the ataxia telangiectasia and rad3-related-checkpoint kinase 1 DNA damage response axis in colon cancers' have been presented. "In response to certain types of DNA damage, ataxia telangiectasia and rad3-related (ATR) phosphorylates checkpoint kinase 1 (CHEK1) resulting in cell cycle arrest and subsequent DNA repair. ATR and CHEK1 contain mononucleotide microsatellite repeat regions, which are mutational targets in tumors with defective mismatch repair (MMR)," researchers in the United States report. "This study examined the frequency of such mutations in colon cancers and their impact on biologic behavior. Screening for ATR mutations in 48 tumors was performed using denaturing high-performance liquid chromatography (DHPLC) and confirmed with sequencing analysis. The CHEK1 exon 7 A(9) region was sequenced in 20 of the 27 (74%) tumors with high frequency of microsatellite instability (MSI-H). Univariate and multivariate analyses were used to examine associations with clinical outcomes. Frequent mutations in MSI-H colon cancers were identified within the ATR (37%)/CHEK1(5%) damage response pathway. Stage and MSI status both independently predicted overall survival (OS) and disease-free survival (DFS). ATR status was not associated with stage, but was associated with a trend toward improved DFS: 0/9 cancers recurred in MSI-H cases harboring ATR mutations vs. 4/18 recurrences in MSI-H cases without ATR mutations," wrote K.A. Lewis and colleagues, Mayo Clinic. The researchers concluded: "This suggests that ATR mutations may affect clinical behavior and response to therapy in MSI-H colon cancers." Lewis and colleagues published their study in Genes, Chromosomes, and Cancer (Mutations in the ataxia telangiectasia and rad3-related-checkpoint kinase 1 DNA damage response axis in colon cancers. Genes, Chromosomes, and Cancer, 2007;46(12):1061-8). For additional information, contact K.A. Lewis, Mayo Clinic, Dept. of Gynecologic Oncology, Rochester, MN 55905 USA.. Publisher contact information for the journal Genes, Chromosomes, and Cancer is: Wiley-Liss, Division John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA. Keywords: United States, Rochester, Ataxia-telangiectasia, Colon Cancer, Colon Carcinoma, DNA Damage, DNA Research, Deoxyribonucleic Acid, Dermatology, Enzyme Research, Genetics, Kinase, Neurology, Oncology, Proteomics, Telangiectasia. This article was prepared by Clinical Oncology Week editors from staff and other reports. Copyright 2007, Clinical Oncology Week via NewsRx.com.
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