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ORIGINAL ARTICLE |
1 Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S. P.Mukherjee Road, Calcutta: 700026, India
2 Department of Pathology, Bankura Sammilani Medical College, Bankura, West Bengal, India
3 Department of Human Genetics, Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Calcutta-700032, India
Correspondence to:
Dr C K Panda, Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Calcutta-700026, India;
ckpanda{at}vsnl.net
Background: Deletions in chromosome 3 occur frequently in uterine cervical carcinoma (CA-CX). The common consensus regions deleted during CA-CX development are not well defined, and have not been correlated with tumour progression.
Aims: To define specific regions of chromosome 3 deleted during development of CA-CX and to correlate these with clinicopathological data.
Methods: Deletion mapping of chromosome 3 was done in seven cervical intraepithelial neoplasia (CIN) and 43 primary CA-CX samples using 20 highly polymorphic microsatellite markers.
Results: Deletions of chromosome 3 were significantly associated with tumour progression. High frequencies (33–53%) of loss of heterozygosity (LOH) were found in 3p26.1, 3p22.3, 3p21.2, and 3p13, suggesting the location of putative tumour suppressor genes (TSGs) in these regions. Among these four regions, deletions in 3p21.2 were suggested to occur early during CA-CX development. A significant correlation was found between LOH at 3p26.1 and 3p22.3 with tumour progression from stage I/IIB to stage III/IV. No association was found with the highly deleted regions and human papillomavirus positivity, parity, or menopausal status. Microsatellite size alteration was seen in only seven of the samples. However, rare biallelic alterations were seen in and around the highly deleted regions. Loss of normal copy of chromosome 3 and interstitial alterations in chromosome 3p were seen in some samples.
Conclusion: These four regions on chromosome 3p may be differentially deleted during specific stages of CA-CX development. The putative TSGs located in these regions may have a cumulative effect on tumour progression.
Keywords: squamous cell carcinoma of the uterine cervix; chromosome 3 alterations; tumour suppressor gene(s); human papilloma virus infection
Abbreviations: CA-CX, uterine cervical carcinoma; CIN, cervical intraepithelial neoplasia; FAL, fractional allele loss; HPV, human papillomavirus; LOH, loss of heterozygosity; MA, microsatellite size alteration; PCR, polymerase chain reaction; RCC, renal cell carcinoma; RFLP, restriction fragment length polymorphism; TSG, tumour suppressor gene
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