University of Khartoum

Loss of Heterozygosity and Microsatellite Instability in Sudanese Colorectal Cancer

Loss of Heterozygosity and Microsatellite Instability in Sudanese Colorectal Cancer

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Title: Loss of Heterozygosity and Microsatellite Instability in Sudanese Colorectal Cancer
Author: ELFATEH, OMMNIYAH; ELTAYEB, MUNTASER
Abstract: Microsatellite instability (MSI) and loss of heterozygosity (LOH) are observed in colorectal cancers (CRCs) and are attributed to defects in Mismatch Repair (MMR) genes. Mismatch repair deficiency allows for accumulation of mutations in the tandem repeats of key target genes, which may be involved in the initiation and progression of MSI to CRC. In addition to MSI, CIN represent another tumorigenesis pathway. In this study, BAT26 marker was chosen for its high specificity and sensitivity, to detect microsatellite instability in 42 colorectal tumors using PCR. Microsatellite analysis showed MSI or Loss of Herterozygosity (LOH) in 31% (14 out of 42) CRC patient. LOH was detected in 78% (11 out of 14), while MSI was observed in 21% (3 out of 14) Most of the LOH and MSI cases were familial 58% (7 out of 12), under 50 years old 64 % (9 out of 14). One hundred and ninety four (194) genes - DNA repair/ genome stability, and apoptosis signaling - were analyzed using macroarray technique to highlight candidate CRC genes. Results showed a 1.5 fold higher expression (as compared to controls) of genes that participate in Mismatch Repair (MMR), Base Excision Repair (BER), Recombination repair, and other genome stability genes. We concluded that LOH and Microsatellite instability plays a critical role in Sudanese CRC. The marker BAT26 is recommended to be use as screening tool for familial and inherited CRC syndromes. A scenario of tumourogenesis process was hypothesized in the light of macoarray results.
URI: http://hdl.handle.net/123456789/6408
Date: 2007-07


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