Mechanisms of FHIT Gene Fragility in Human Cancers Induced by Carcinogens

致癌物诱发人类癌症中FHIT基因脆性的机制

• 批准号: 6570498
• 负责人: CARLO M CROCE
• 金额: $ 15.13万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6570498
• 关键词: cell line; cervix neoplasms; chemical carcinogen; chemical carcinogenesis; disease /disorder etiology; environment related neoplasm /cancer; environmental toxicology; esophagus neoplasm; gastrointestinal neoplasms; gene deletion mutation; gene rearrangement; human genetic material tag; human tissue; lung neoplasms; molecular cloning; neoplasm /cancer genetics; nucleic acid repetitive sequence; smoking; tobacco abuse; tumor suppressor genes

DESCRIPTION: (Applicant's Description) We propose to determine the mechanisms of FHIT gene rearrangements in human cancers by sequencing the entire region of the FHIT gene involved in the breaks and by cloning and sequencing breakpoints involved in lung, esophageal, gastrointestinal and cervical cancer. Since the FHIT gene is the target for rearrangements in tumors induced by either chemicals such as benzopyrene present in cigarette smoke or biological agents, such as human papillomaviruses, we will compare the sequences of breakpoints in lung cancer and cervical cancers to establish whether the breakpoints involve the same regions or different regions and whether the same or different repetitive elements flank the breakpoints in these tumors. If we establish that the breakpoints in lung cancer cluster within discrete regions of the FHIT gene we will compare the DNA sequence of these regions in smokers that have developed lung cancer before the age of forty and in smoking centenarians who have not developed lung cancer. This investigation could provide important information on the role of the FHIT gene in cancer predisposition. In parallel, we will determine the sequence and structure of the human NIT gene and locus in tumors, and sequence FHIT interacting gene loci isolated by Project 1.

描述：(申请人描述)我们建议确定 FHIT基因重排在人类肿瘤中的作用机制 参与断裂的FHIT基因的整个区域，并通过克隆和 涉及肺、食道、胃肠道和 宫颈癌。 由于FHIT基因是由FHIT基因引起的肿瘤重排的靶 要么是香烟烟雾中存在的苯并[2]等化学物质，要么是生物 例如人类乳头瘤病毒，我们将比较它们的序列 肺癌和宫颈癌的断点，以确定是否 断点涉及相同的区域还是不同的区域以及是否相同 或者在这些肿瘤的断裂点两侧有不同的重复元件。如果我们 确定肺癌的断点集中在离散的区域内 我们将比较吸烟者这些区域的DNA序列 在40岁之前患上肺癌和吸烟的人 没有患上肺癌的百岁老人。这项调查可能 提供有关FHIT基因在癌症中的作用的重要信息 性情。 同时，我们将确定人类NIT的序列和结构 在肿瘤中的基因和基因座，以及通过 项目1。