NF1 gene loss of heterozygosity and expression analysis in sporadic colon cancer (CROSBI ID 107911)
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Čačev, Tamara ; Radošević, Senka ; Spaventi, Radan ; Pavelić, Krešimir ; Kapitanović, Sanja
engleski
NF1 gene loss of heterozygosity and expression analysis in sporadic colon cancer
Colon cancer tumorigenesis is a multistep process of mutation accumulation in a number of oncogenes and tumor suppressor genes. NF1 gene protein, neurofibromin, acts as a tumor suppressor by turning the active form of Ras into inactive one. This molecular switch has an important role in the control of the cell cycle and differentiation and changes in Ras activity are present in many different cancers. This is the first study to investigate the role of NF1 gene in sporadic colon cancer. We investigated the loss of heterozygosity (LOH) at the NF1 gene locus in 100 sporadic colon cancers. Real-time RT-PCR was used to determine NF1 mRNA expression in tumors and corresponding normal mucous tissue. Relative ratio of NF1 mRNA type I and II isoforms expression was examined as well. The results were correlated with the patients' clinicopathological features. LOH of NF1 gene was detected in 20.7% of informative samples. NF1 gene expression was significantly increased in tumor tissue compared to corresponding normal tissue (p=0.04291). There was a statistically significant increase of NF1 mRNA type I isoform expression (p=0.0005) in tumor tissue when compared to corresponding normal colon tissue. NF1 mRNA isoform type II was dominantly expressed in normal tissue, while the NF1 mRNA isoform type I prevailed in tumor samples. In several tumor pairs analyzed NF1 mRNA isoform type I and II expression in normal mucous tissue at variable distances from the tumor and we detected a transition from dominant expression of isoform type II in normal mucous tissue 15 cm away from the tumor to dominant expression of isoform type I in tumor tissue itself.
NF1 gene; LOH; mRNA expression; isoform type I and II expression; sporadic colon cancer
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