Genomic deletion and p53 inactivation in cervical carcinoma.
The tumor-suppressor gene p53 acts as "the guardian of the genome", sensing DNA damage and initiating protective responses. To examine the hypothesis that p53 abnormality leads to increased genomic alterations in primary tumor cells, our study utilized 51 primary tumors of cervical carcinoma and 10 microsatellite markers. These markers were mapped to the short arms of chromosomes 3 and 5, covering the regions 3p13-25 and 5p15.1-15.3. Genomic deletion on 3p and 5p was correlated with genetic or epigenetic p53 inactivation pathways, including p53 mutation, genetic deletion of p53 and cervical infection with human papillomavirus. The proportion of abnormal p53 was found to be significantly higher in the cases exhibiting loss of heterozygosity (LOH) on 5p (p < 0.001), supporting the hypothesis of the presence of a p53-dependent pathway to cervical tumorigenesis. In contrast, however, LOH on 3p was found to be independent of p53 inactivation. A common deletion region, 3p22-24, was identified in 44% of informative cases, and genomic loss at this specific region was correlated with early tumorigenic onset and poor grade of tumor differentiation. Diversity within the patterns of genomic alteration in the same form of cancer suggests different sets of risk/tumorigenic profiles, molecular pathogenesis, as well as prognosis and outcome.
Ku
W H
WH
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Liu
I L
IL
Yen
M S
MS
Chang Chien
C C
CC
Yue
C T
CT
Ma
Y Y
YY
Chang
S F
SF
Ng
H T
HT
Wu
C W
CW
Shen
C Y
CY
D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000235:genetics*; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D002895:Chromosomes, Human, Pair 5; D005260:Female; D017353:Gene Deletion; D015894:Genome, Human; D006801:Humans; D008875:Middle Aged; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics*
D016159:Tumor Suppressor Protein p53