Analysis of molecular alterations in chromosome 8 associated with the development of uterine cervical carcinoma of Indian patients.
OBJECTIVE
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.
Bhattacharya
N
N
Chittaranjan National Cancer Institute, Kolkata-700 026, India.
Singh
R K
RK
Mondal
S
S
Roy
A
A
Mondal
R
R
Roychowdhury
S
S
Panda
C K
CK
D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D016259:Genes, myc / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India; D019656:Loss of Heterozygosity; D008875:Middle Aged; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology