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Distinct Series of mutations of conserved regions of TP53 in patients with colorectal cancer in the population of Kashmir: an emerging high-risk area
S. Rehman, Sameer s. r., Zahoor l., s. Abdullah, z. r. Shah, d. Afroze, i. Hussain, s. m. Syeed Shaffi, n., m. r. Rizvi and m. r. Siddiqi
FUND: colorectal cancer (CRC), is a leading cause of mortality and morbidity. Valley of kashmir, Northern India, has been described as a high risk area for colorectal cancer. AIM: the aim was to make a preliminary attempt to study the mutations in exons 5-8 (the DNA binding domain) tumor suppressor gene in 42 patients TP53, CRC of Kashmir. Materials and methods: The study population consisted of 42 patients diagnosed a colorectal cancer. TP53 gene exons 5 8 were detected by means of a single strand conformation polymorphism (SSCP). All samples that showed the band different models of migration in the SSCP were confirmed by sequencing. Results: The 28 mutations were found in TP53 gene in 19 patients, including 23 replacements (17 transitions + 6 transversions) and five postings. Replacements 23 represent 18 missense mutations, bringing to aminoacidiche, 2 nonsense mutations that lead to stop codons, while the remaining 3 were silent mutations. Inserts five represented frame-shifts. Two of the 28 mutations (7.14%) have not been previously declared in samples from colorectal cancer and have been identified as novel TP53 mutations. Comparison of mutation profile with other ethnic populations and regions reflects both the differences and similarities that indicates the co-exposure to a single set of risk factors.CONCLUSIONS: The TP53 gene mutation is one of the most common mutation in the development of colorectal cancer. high frequency TP53 gene mutations involves TP53 as predominant factor for colorectal cancer in Kashmiri ethnic population at high risk.
Volume: 3 article number: 129 DOI: 10.3332/ecancer may.2009.129 received: 01/11/2008 published: 09/01/2009
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Epigenetic inactivation gene NORE1 correlates with malignant Colorectal tumor progression
NORE1 (RASSF5) is a member of a newly described RASSF family from Cape Executive expression is often inactivated NORE1 on aberrant promoter gipermetilirovan in many cancers, suggesting that it may be alleged supressora NORE1. However, the expression and mutation status NORE1 and its involvement in colorectal suffered mutations.
Expression, mutation and methylation status NORE1A NORE1B in 10 cancer and cell lines and primary tumor showed 80 quantitative PCR, SSCP and DNA sequence bisulfite. Effect on expression and NORE1B NORE1A tumor cell growth by using cell number counting, flow cytometry and colony formation tests.
Expression NORE1A and NORE1B transcript easily detectable in all normal colonic epithelial tissues, but was significantly reduced in 7 (70%)and 4 (40%) 10 cancer cell lines and 31 (38.8%)and 25 (80 primary carcinoma 31.3) tissue, respectively. 46 (57.6%)and 38 80 mapped 47.5% tissue collections exhibited tumors and specific reduction NORE1A NORE1B. advanced and high grade tumors compared with early and low grade tumors are abnormal reduction in somatic mutations NORE1. Although the gene have been identified, the recreated all cells after treatment with low expressor demethylating Agent 5-AZA dC. analysis of DNA sequences bisulfite 31 CpG sites in the region, the promoter has demonstrated that anomalous decrease NORE1A is closely related to the promoter CpG sites gipermetilirovan. Furthermore transitional expression and siRNA mediated knockdown analyses showed that both NORE1A and NORE1B reduce cellular growth and colony formation ability of cancer cells and cancer cells respond to apoptotic stress.
Our data show that the epigenetic inactivation NORE1 due to abnormal promoter gipermetilirovan is a common event in colorectal suffered mutations and could be involved in malignant Colorectal tumor progression.
cancer3 