Cellular gene expression in HPV associated neoplasia

HPV相关肿瘤中的细胞基因表达

基本信息

批准号：
6515079
负责人：
Christopher Paul Crum
金额：
$ 8.48万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-07-23 至 2004-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6515079
关键词：
cervical /vaginal smear cervix neoplasms clinical research complementary DNA epithelium female gene induction /repression human papillomavirus human subject immunocytochemistry neoplasm /cancer genetics polymerase chain reaction restriction fragment length polymorphism virus genetics virus related neoplasm /cancer women's health

项目摘要

This application proposes a study to identify genes that are preferentially up-regulated in human papillomavirus(HPV)-associated cervical neoplasia for the purpose of creating reagents for the diagnosis of pre- invasive cervical neoplasia. This will entail the critical analysis of approximately 80 genes that have been identified in a prior comparison of expression arrays generated from two cervical carcinomas and three control tissues, including normal transformation zone, normal portio epithelium; and atrophic squamous cells. These genes, all of which demonstrated at least ten fold higher expression values over controls, will be studied further by the hybridization of secondary arrays containing these genes to radioactive probes generated from neoplasia- derived RNAs. Genes which alone or together are consistently up- regulated in neoplastic tissues will be studied by immunohistochemical analysis of tissue arrays containing a series of tissues which span the spectrum of cervical neoplasia and for which the HPV status and type have been determined. Finally, candidate genes will be assembled into smaller arrays and hybridized with radioactive cDNA probes from RNAs derived from exfoliated cervical samples in which the cytologic and viral (HPV) status have been determined. The last exercise is designed to determine the potential diagnostic value of selected genes in predicting the presence of HPV- positive cytologic abnormalities. These studies have broad implications for the future of testing women for preinvasive and invasive cervical neoplasia, and seek to identify methods of detecting cervical neoplasia that circumvent the potential limitations of cytologic screening (sensitivity) and HPV testing (specificity). Such methods, if successful, could conceivably revolutionize the approach to cervical cancer prevention by broadening the conditions under which screening could be conducted.

本申请提出了一项研究，以鉴定在人乳头瘤病毒（HPV）相关宫颈肿瘤中优先上调的基因，以创建用于诊断浸润前宫颈肿瘤的试剂。这将需要对大约 80 个基因进行关键分析，这些基因是在先前比较从两个宫颈癌和三个对照组织（包括正常转化区、正常部分上皮）产生的表达阵列中鉴定的；和萎缩的鳞状细胞。这些基因均表现出比对照高至少十倍的表达值，将通过含有这些基因的二级阵列与由肿瘤衍生的RNA产生的放射性探针杂交来进一步研究。将通过组织阵列的免疫组织化学分析来研究肿瘤组织中单独或一起持续上调的基因，所述组织阵列包含一系列跨越宫颈肿瘤谱系的组织，并且已确定其HPV状态和类型。最后，候选基因将被组装成更小的阵列，并与来自脱落宫颈样本的 RNA 的放射性 cDNA 探针杂交，其中细胞学和病毒 (HPV) 状态已确定。最后一个练习旨在确定所选基因在预测 HPV 阳性细胞学异常存在方面的潜在诊断价值。这些研究对未来检测女性浸润前和浸润性宫颈肿瘤具有广泛的影响，并寻求确定检测宫颈肿瘤的方法，以规避细胞学筛查（敏感性）和 HPV 检测（特异性）的潜在局限性。此类方法如果成功，可能会扩大筛查条件，从而彻底改变宫颈癌预防方法。