Genetic Alterations at Chromosome 6 Associated with Cervical Cancer Progression
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Loss of heterozygosity (LOH) analysis on chromosome 6 was performed to define the genetic changes that occur in the development of squamous cell cervical cancer (SCC). Detailed analysis with 28 microsatellite markers revealed several loci with high frequency of deletions at the short (6p25, 6p22, 6p21.3) and long (6q14, 6q16–q21, 6q23–q24, 6q25, 6q27) arms of chromosome 6. Examination of microdissected 37 SCC and 22 cervical intraepithelial neoplasias (CIN) revealed allelic deletions in the HLA class I–III region (6p22–p21.3) and at subtelomeric locus 6p25-ter in more than 40% of CIN. By a combination of LOH and microdissection of multiple samples from the same tumor sections, we studied the intratumoral genetic heterogeneity of SCC, and identified clonal and subclonal allelic deletions. Half of SCC had clonal allelic deletion at D6S273, which is localized in intron of Ly6G6D (MEGT1) gene mapped in the HLA class III region. The LOH frequency at 6q in CIN cases did not exceed 20%. Allelic deletions at two loci, 6q14 and 6q16–q21, were for the first time associated with invasion and metastasis in SCC.
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