H-ras codon 12 mutation in cervical dysplasia

A mutation in codon 12 of the H-ras oncogene has been implicated in the pathogenesis of cervical cancer. To determine if mutational activation of H-ras is an early event in carcinogenesis, we looked for the presence of codon 12 H-ras mutation in precancerous cervical dysplasia. We analyzed cervical DNA from 63 normal patients and 72 patients with biopsy-proven cervical dysplasia [CIN I (48), CIN II (9), CIN III (15)]. HPV typing was performed on these samples by Viratype and analysis and polymerase chain reaction (PCR). To detect H-ras codon 12 mutation, DNA was isolated and amplified by PCR with primers for H-ras. A unique restriction site for MspI contained within the wild-type ras PCR product allows discrimination between unmutated and mutated sequences. Restriction enzyme analysis with MspI was performed on PCR products to distinguish between wild-type and mutated sequences. HPV 16 or 18 was present in 33% of CIN I, 56% of CIN II, and all CIN III samples. No codon 12 mutations were detected in any sample. We conclude that while HPV is associated with cervical dysplasia and its prevalence increases in more advanced lesions, it is unlikely that H-ras codon 12 mutations are an early occurrence in the progression of precancerous lesions to cervical carcinoma.