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Host genomic alterations in addition to human papillomavirus (HPV) are neededfor cervical precursor lesions to progress to invasive cancer because only a smallpercentage of women infected by the virus develop disease. However, the genomicalterations during the progression of cervical lesions have not been systematicallyexamined. The aim of this study was to identify differential genomic alterationsamong cervical intraepithelial neoplasia CIN1, CIN2, CIN3 and cervical squamouscell carcinoma (SCC). Genomic alterations were examined for 15 cases each of CIN1,CIN2, CIN3 and SCC by array-based comparative genomic hybridization (array CGH).The chromosomal regions showing significant differential in DNA copy number aberrations(DCNAs) among CIN1, CIN2, CIN3 and SCC were successfully identified by resampling-basedt-test. The chromosomal regions of 5q35.3 and 2q14.3 showed significant DCNAsbetween CIN1 and CIN2, and between CIN2 and CIN3, respectively, while a significantdifference in DCNAs between CIN3 and SCC was observed at 1q24.3, 3p14.1, 3p14.2,5q13.2, 7p15.3, 7q22.1 and 13q32.3. In addition, the status of DCNAs in 1q43,2p11.2, 6p11.2, 7p21.1, 7p14.3, 10q24.1, 13q22.3, 13q34 and 16p13.3 was conservedthroughout the progression of CIN to SCC. The presence of differential and commonDCNAs among CIN1, CIN2, CIN3 and SCC supports that the CIN progression may includecontinual clonal selection and evolution. This approach also identified 34 probesets consistently overexpressed when amplified, suggesting an unbiased identificationof candidate genes in SCC during cervical cancer progression.

Differential DNA copy number aberrations in the progression of cervical lesions to invasive cervical carcinoma