SEQUENCE VARIATION OF HUMAN PAPILLOMAVIRUS TYPE-16 E7 IN PREINVASIVE AND INVASIVE CERVICAL NEOPLASIAS

Variation in the nucleotide sequence of the HPV 16 E7 gene in preinvas ive cervical intraepitherial neoplasia (CIN) and invasive cervical car cinoma specimens was analyzed. Direct DNA sequencing of PCR-amplified products with primers different fram those used for PCR with 5'-end la beling generated distinct sequence ladders with a low background, even in specimens containing relatively low copy numbers of HPV. Of 14 cer vical neoplasias, II cases showed sequence diversity from prototype HP V16, and a total of 22 nucleotide exchanges were detected. Nine of the se led to single amino acid exchanges: [Thrs] to [Lys(5)] in one case and [Asn(29)] to [Ser(29)] in eight cases. The [Ser(29)] E7 was distri buted uniformly among invasive carcinomas and precancerous legions, an d was also found in a normal cervix. The [Lys(5)] E7 and [Ser(29)] E7 had transforming potential similar to the prototype E7 assessed by coo peration with the activated I as gene in rat embryo fibroblasts.