Mapping common deleted regions on 5p15 in cervical carcinoma and their occurrence in precancerous lesions

Molecular Cancer

关键词: Cervical carcinoma;    cervical intraepithelial neoplasia;    chromosome 5p;    loss of heterozygosity;    deletion mapping;    human papilloma virus;   

DOI  :  10.1186/1476-4598-1-3

来源: DOAJ

【 摘 要 】

Abstract

Background

Previous studies have shown that the short arm of chromosome 5 (5p) exhibit frequent genetic changes in invasive cervical carcinoma (CC), and that these changes arise early during the carcinogenesis, in precancerous lesions. These data therefore suggest that loss of candidate tumor suppressor genes located on 5p is associated with the development of CC. However, the precise location of 5p deletions is not known.

Results

We performed a detailed deletion mapping of 5p in 60 cases of invasive CC. We found that 60% of the tumors exhibit a 5p loss of heterozygosity (LOH). The patterns of LOH allowed us to identify two minimal regions of deletions, one at 5p15.3 spanning a 5.5 cM genetic distance and a second site of 7 cM at 5p15.2-15.3. In addition, we also identified 5p deletions in 16% lesions of high-grade cervical intraepithelial neoplasia (CIN). 5p LOH was found in 63% of HPV 16 positive tumors, while only 33% tumors with other HPV-types had 5p LOH. The differences in frequency of 5p LOH between tumors harboring HPV16 in combination with other HPV types and tumors harboring HPV16 DNA alone were significantly higher, suggesting a synergistic effect of high-risk types in causing genomic instability.

Conclusion

These findings implicate the presence of tumor suppressor gene(s) on 5p relevant to CC tumorigenesis.

【 授权许可】

Unknown