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


CONCLUSIONS
These findings implicate the presence of tumor suppressor gene(s) on 5p relevant to CC tumorigenesis.
Arias-Pulido
Hugo
H
Department of Pathology, College of Physicians & Surgeons of Columbia University, 630 West 168th Street, New York, 10032, USA. harias59@yahoo.com
Narayan
Gopeshwar
G
Vargas
Hernan
H
Mansukhani
Mahesh
M
Murty
Vundavalli V V S
VV
D045744:Cell Line, Tumor; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D027383:Papillomaviridae / Q000502:physiology; D020161:Physical Chromosome Mapping; D011230:Precancerous Conditions / Q000235:genetics* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology