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

HPV阳性宫颈癌预防和治疗的分子流行病学研究

基本信息

批准号：
08671872
负责人：
YOSHIKAWA Hiroyuki
金额：
$ 1.47万
依托单位：
University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671872/
关键词：
HUMAN PAPILLOMAVIRUS (HPV)CERVICAL CANCER HPV DNA ANTIBODY AGAINST HPV FHIT GENE P53 HPVDNA FHTT遺伝子 HPV(ヒトパピローマウイルス)VLP抗体 CIN HPV型患者年令組織型予後

项目摘要

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

1)为探讨FHIT基因异常表达与宫颈癌发生发展的关系，采用RT-PCR和cDNA测序方法检测了32例宫颈癌及其18例宫颈癌前病变（CIN）中FHIT基因的表达，并探讨了FHIT基因表达与HPV感染及其他临床特征的关系。我们在32例浸润性宫颈癌中检测到11例（34%）异常FHIT转录，在14例高级别CIN（CIN 2/3）中检测到5例（36%）异常FHIT转录。FHIT基因在浸润性癌和CIN中的表达是一致的。在异常FHIT转录物中，外显子5、6和7通常缺失，伴有或不伴有外显子4和/或8的缺失。FHIT基因的变异频率与HPV的类型和存在无关。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突变仅见于0-6%的宫颈癌。根据最近的研究表明， ...更多信息鉴于外阴癌是一种老年妇女的疾病，是已知的HPV相关恶性肿瘤，p53基因突变率超过20%，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。应用PCR单链构象多态性（SSCP）和DNA测序技术分析p53基因突变。46例宫颈癌中5例（11%）p53基因点突变，17例中1例（6%）为高危型HPV（HPV 16和HPV 18），27例中4例（15%）为中危型HPV。突变的残基位于被称为DNA结合结构域的选择性序列中。p53基因突变均为过渡型，提示突变可能是由内源性突变引起的。提示p53基因突变，尤其是沿着中危型HPV的突变，可能是老年妇女宫颈癌的发病因素之一。少