Analysis of mutations in the E6/E7 oncogenes and L1 gene of human papillomavirus 16 cervical cancer isolates from China.
Human papillomavirus type 16 (HPV16) has a number of intratypic variants; each has a different geographical distribution and some are associated with enhanced oncogenic potential. Cervical samples were collected from 223 cervical cancer patients and from 196 age-matched control subjects in China. DNA samples were amplified by using primers specific for the E6, E7 and partial L1 regions. Products were sequenced and analysed. It was found by using a PCR-sequence-based typing method that HPV infection rates in China were 92.8 % in cervical cancer patients and 15.8 % in healthy controls. HPV16 was detected in 70.4 % of cervical cancer patients and in 6.1 % of controls. In HPV16-positive cervical cancers, 23.6 % belonged to the prototype, 65.5 % were of the Asian variant, 5.5 % were of African type 1 and 3.6 % were European variants, whilst only one was a new variant that differed from any variant published so far. Prevalences of HPV16 E6 D25E and E113D variants were 67.3 and 9 %, respectively. In addition to D25E and E113D, the following E6 variations were found in this study: R129K, E89Q, S138C, H78Y, L83V and F69L. The results also showed that the prevalences of three hot spots of E7 nucleotide variation, N29S, S63F and a silent variation, nt T846C, were 70.2 % (33/47), 51.1 % (24/47) and 61.7 % (29/47), respectively. The following L1 variations were found in this study: S377A, K387E, E378D, K382E and T379P. It was also found that the average age of Asian variant-positive cervical cancer patients (42.98+/-10.43 years) was 7.56 years lower than that of prototype-positive patients (50.54+/-10.91). It is suggested that the high frequency of HPV16 Asian variants might contribute to the high incidence of cervical cancer in China.
Wu
Yuping
Y
State Key Laboratory of Biocontrol, Key Laboratory of Genetic Engineering of MOE, Department of Biochemistry, School of Life Sciences, Sun Yat-Sen (Zhongshan) University, Guangzhou 510275, People's Republic of China.
Chen
Yulong
Y
State Key Laboratory of Biocontrol, Key Laboratory of Genetic Engineering of MOE, Department of Biochemistry, School of Life Sciences, Sun Yat-Sen (Zhongshan) University, Guangzhou 510275, People's Republic of China.
Li
Longyu
L
Department of Oncology, Maternal and Child Health Hospital of Jiangxi Province, Nanchang, People's Republic of China.
Yu
Guifang
G
Department of Gynecology, People Hospital of Zhuhai, Guangdong Province, People's Republic of China.
He
Ying
Y
State Key Laboratory of Biocontrol, Key Laboratory of Genetic Engineering of MOE, Department of Biochemistry, School of Life Sciences, Sun Yat-Sen (Zhongshan) University, Guangzhou 510275, People's Republic of China.
Zhang
Yanling
Y
Department of Oncology, Maternal and Child Health Hospital of Jiangxi Province, Nanchang, People's Republic of China.
D036022:Capsid Proteins / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000821:virology*; D002681:China; D005260:Female; D005814:Genes, Viral; D052162:Human papillomavirus 16 / Q000145:classification / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D012307:Risk Factors; D013045:Species Specificity; D002583:Uterine Cervical Neoplasms / Q000821:virology*
D036022:Capsid Proteins; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; C062495:oncogene protein E7, Human papillomavirus type 6; C063317:L1 protein, Human papillomavirus type 16; D011505:Protein-Tyrosine Kinases