MOLECULAR EPIDEMIOLOGICAL STUDY FOR PREVENTION AND TREATMENT OF HPV-POSITIVE CERVICAL CANCER

1)为探讨FHIT基因异常表达在宫颈癌发生发展中的作用，我们采用RT-PCR和DNA测序法检测了32例宫颈癌及其18例癌前病变组织中FHIT基因的表达，并探讨了FHIT基因表达与HPV感染等临床特征的关系。在32例浸润性宫颈癌中11例(34%)和14例高级别宫颈上皮内瘤变(CIN 2/3)中检出5例(36%)FHIT转录本。在浸润性癌和CIN中，FHIT基因的警报是相同的。在异常的FHIT转录本中，外显子5、6和7通常缺失或不伴有外显子4和/或8的缺失。FHIT基因突变频率与HPV类型及存在与否无关。FHIT基因的异常表达可能在宫颈癌的早期发展中起重要作用。2)P53基因突变仅在0-6%的宫颈癌中发现。根据最近的研究表明，…我们分析了46例60岁以上(平均71岁，范围60~96岁)宫颈癌患者的P53基因突变情况。采用单链构象多态(SSCP)和DNA测序技术分析p53基因突变情况。P53基因点突变在46例宫颈癌中检出5例(11%)，其中高危型HPV16和HPV18型1例(6%)，中危型HPV27例(15%)。突变的残基位于称为DNA结合域的选择性序列中。所有观察到的P53基因突变均为过渡型，提示该突变可能是由内源性突变引起的。这些数据表明，p53基因突变，特别是与中危HPV类型一起，可能是影响老年妇女宫颈癌的致病因素之一。较少

1) To investigate involvement of aberrant expression of the FHIT gene in development of cervical carcinoma, we examined the FHIT gene expression by the RT-PCR and cDNA sequence method in 32 cervical carcinomas and 18 its precursor lesions (CINs) and investigated relation of the FHIT gene expression to HPV infection and the other clinical characteristics. We detected the aberrant FHIT transcrtipts in 11 of 32 (34%) invasive cervical carcinoma and in 5 of 14 (36%) high-grade CINs (CIN 2/3). The alerations of the FHIT gene was identical in invasive carcinomas and CINs. The exons 5, 6 and 7 were commonly absent with or without loss of exon 4 and/or 8 in the aberrant FHIT transcripts. The alteration frequency of the FHIT gene was not related to HPV type and presence. Aberrant expression of the FHIT gene may have an important role in the early phase of development of cervical carcinoma.2) The p53 mutation has been found only in 0-6% of cervical carcinomas. In light of recent studies demonstr … More ating that mutation of p53 gene was found in over 20% of the patients with vulvar carcinoma, a disease of elder women and a known HPV-related malignancy, we analyzed mutation of p53 gene in 46 women with cervical carcinomas at the age of 60 or more (mean ; 71 years, range ; 60-96 years). Mutation of the p53 gene was analyzed by PCR-based single-strand conformation polymorphism (SSCP) and DNA sequencing technique. Point mutation of p53 gene was detected in 5 out of 46 (11%) cervical carcinomas : 1 of 17 (6%) samples associated with high-risk HPVs (HPV 16 and HPV 18) and 4 of 27 samples (15%) with intermediate-risk HPVs. The mutated residues resided in the selective sequence known as a DNA binding domain. All of the observed mutations of p53 gene were transition type, suggesting that the mutation may be caused by endogenous mutagenesis. These data imply that p53 gene mutation, particularly along with intermediate-risk HPV types, may constitute one of pathogenetic factors in cervical carcinoma affecting elderly women. Less