Although, cytogenetic studies on cervical cancer have identified a number of non-random karyotipic changes involving chromosomes 1, 3, 5, 17, and X, the search for the critical genetic changes has been hampered by technical difficulties, such as the karyotypic complexity of this tumor. The advent of comparative genomic hybridization has opened a novel means of characterizing genomic imbalances and to date several studies have identified 3q gain, which occurred at severe dysplasia/carcinoma in situ.
This lead to the suggestion that this genetic aberration plays a role in the transition from dysplasia to invasive cervical cancer (57,58). A number of studies in this region have identified the candidate oncogenes, such as PIK3CA, which encodes a catalytic subunit of phosphatidylinsitol 3-kinase and has been already implicated in ovarian and cervical carcinomas (59).
Other chromosomal changes involve loss of 2q, 3p, 4p, 4q, 5q, 6q, 11q, 13q, and 18q regions and gain of 1q, 3q, 5p, and 8q at various stages of cervical cancer (60). LOH was also frequently found at 3p, 4p, 4q, 5p, 6p, 6q, 11q, and 17p chromosomal regions, suggesting the presence of putative tumor suppressor genes on these chromosomes (61). The TSLC1 gene (also known as IGSF4 or NECL-2) might be one of the candidate suppressors of tumorigenicity on chromosome 11. This gene, which maps at 11q23, encodes an immunoglobulin-like cell surface protein that belongs to the nectin and nectin-like family of proteins and is involved in cell-cell adhesions. TSLC1 was found to be silenced in 91% (10/11) of cervical cancer cell lines, mostly as a result of promoter hypermethylation alone or combined with allelic loss. Promoter hypermethy-lation was also present in 58% of cervical carcinomas and 35% of high-grade CIN lesions, but not in low-grade CIN lesions and normal cervix (62). However, ectopic expression of TSLC1 is able to suppress only anchorage-independent growth of SiHA cells, suggesting that these cells become tumorigenic as a result of an additional hit.
Recurrent sites of amplification were noted at 11q13, 11q21, and 19q13.1 and were more commonly associated with HPV18 infection (63). This relationship is interesting in the light of the oncogenic potential of this HPV type, which is known to cause rapid transition to malignancy and to characterize a more aggressive phenotype. Although, amplification of specific genes, as HER-2/neu, has already been shown to predict clinical outcome in cervical cancer (64), the identification of additional genes at specific chromosomal sites are needed to provide new insights into the clinical behavior and management of this tumor.
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