Analysis of molecular alterations in chromosome 8 associated with the development of uterine cervical carcinoma of Indian patients.
OBJECTIVES: We have been done the detailed deletion mapping of chromosome (chr.) 8p21.3-23 to localize the candidate tumor suppressor gene(s) (TSGs) loci as well as studied the mechanism of activation of c-myc gene, located at chr.8q24.1, by analyzing the amplification/rearrangement/HPV integration within approximately 580 kb of c-myc locus in uterine cervical carcinoma (CaCx) of Indian patients. The association between the deletions in chr.8p21.3-23 and alterations in the c-myc locus has also been analyzed. METHODS: The deletion mapping of chr.8p21.3-23 was done by 15 microsatellite markers and the alterations in the c-myc locus were analyzed by Southern hybridization using the pal-1/c-myc/mlvi-4/HPV 16/18 probes in seven cervical intraepithelial neoplasia (CIN) and 55 primary uterine cervical carcinoma. The alterations in chr.8p/q have been correlated with the different clinicopathological parameters. RESULTS: Three discrete minimal deleted regions with high frequencies of loss of heterozygosity (LOH) (37-43%) were identified in the chr.8p23.1-23.2 (D1), 8p23.1 (D2), and 8p 21.3-22 (D3) regions within 0.41-4.62 Mb. The deletion in the D1 region was significantly associated with the deletion in the D2 region (P = 0.03), whereas the deletion in D2 was marginally associated with the deletion in the D3 region (P = 0.07). The alterations in the c-myc locus were seen in 43% of the samples. About 35% of the samples showed coalterations in both arms of chr. 8. No significant association was observed with the alterations in chr.8p/q as well as with the different clinicopathological parameters. CONCLUSIONS: The deletions in chr.8p21.3-23 and the alterations in the c-myc locus are independently associated with the development of CaCx. The D1-D3 regions in chr.8p21.3-23 could harbor candidate TSGs associated with the development of this tumor. The c-myc gene was activated by amplification/rearrangement at the pal-1/c-myc/mlvi-4 loci as well as HPV integration in the pal-1 locus in this tumor.[1]References
- Analysis of molecular alterations in chromosome 8 associated with the development of uterine cervical carcinoma of Indian patients. Bhattacharya, N., Singh, R.K., Mondal, S., Roy, A., Mondal, R., Roychowdhury, S., Panda, C.K. Gynecol. Oncol. (2004) [Pubmed]
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