MAJOR SEQUENCE VARIANTS IN E7 GENE OF HUMAN-PAPILLOMAVIRUS TYPE-16 FROM CERVICAL CANCEROUS AND NONCANCEROUS LESIONS OF KOREAN WOMEN

Geographic specificity of nucleotide sequence variations in the coding and noncoding regions of HPV 16 genome has been reported. Little has been known, however, regarding whether these naturally occurring seque nce variations of HPV 16 may result in marked differences in biologica l properties, such as oncogenic potential. This study was performed to identify sequence variants in the HPV 16 E7 gene derived from Korean women with cervical cancerous and noncancerous lesions, and to assess the association between the sequence variant and the cervical cancer. We examined E7 variants of HPV 16 in a total of 157 patients with no c ervical disease (NCD, n = 87) or cervical neoplasia (cervical intraepi thelial neoplasia 3, n = 21; cervical carcinoma, n = 49), using the ne sted polymerase chain reaction (PCR) and the PCR-directed sequencing m ethods with outer consensus and inner type-specific primers. Forty-two (NCD, n = 9; CIN 3, n = 6; cervical carcinoma, n = 27) of 157 cervica l samples contained HPV 16 E7 DNA, but only 8 had prototype sequences. Four variants of the HPV 16 E7 gene were identified. The variant with a single nucleotide change at position 647 (A --> G, Asn --> Ser) was found in about 60% of DNA samples with HPV 16. The second most common variant, found in 16.7% of cases, had three silent mutations at posit ions 732 (T --> C), 789 (T --> C), and 795 (T --> G). Two other varian ts were detected, one in a patient with cervical cancer and the other in a patient with no cervical disease. One had a single nucleotide cha nge at position 666 (G --> A) and the other had one silent mutation at position 796 (T --> C). The most common variant in Korea has a change of nucleotide affecting the predicted amino acid related with high an tigenicity and binding to retinoblastoma protein. There was a statisti cally significant trend for this variant to be more frequently detecte d in cancerous lesions of the uterine cervix than in noncancerous lesi ons. These data suggest that naturally occurring sequence variants of HPV 16 E7 gene may have different oncogenic properties. (C) 1997 acade mic Press.