CHROMOSOME 18 TUMOR SUPPRESSOR GENES IN ORAL CANCER

口腔癌中的 18 号染色体肿瘤抑制基因

• 批准号: 2696438
• 负责人: THOMAS E. CAREY
• 金额: $ 29.31万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-15 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2696438
• 关键词: chromosome deletion; chromosomes; clinical research; flow cytometry; gene expression; genetic mapping; genetic markers; head /neck neoplasm; human genetic material tag; human subject; human tissue; immunoprecipitation; larynx neoplasms; loss of heterozygosity; metastasis; neoplasm /cancer genetics; neoplasm /cancer invasiveness; neoplastic process; oral pharyngeal neoplasm; polymerase chain reaction; prognosis; squamous cell carcinoma; tissue /cell culture; tumor suppressor genes; western blottings

Squamous cell carcinoma (SCC) of oral cavity is a devastating and deadly disease. At present, there are few definitive indicators for predicting outcome and determining the clinical management other than tumor state and lymph node involvement. Studies over the past two decades have shown that gene defects underlie cancer development and progression, and play a critical role in defining the natural history and biological behavior of cancers. The Principal Investigator has shown that losses affecting the long arm of chromosome 18 (18q) occur in 55-60 percent of oral SCC. The preliminary data indicate that 18q loss is associated with poor prognosis and death from cancer in head and neck SCCs. Moreover, loss of heterozygosity (LOH) on 18q is associated with progression in individual patients. If the Principal Investigator can identify the basis for these findings, then genetic markers could be used in selecting high-risk patients for more aggressive therapy, and spare low risk patients from unnecessary treatment morbidity. Chromosomal regions frequently affected by LOH are thought to indicate the presence of a tumor suppressor gene (TSG) within the affected region. Three candidate TSGs have been identified on 18q; DCC (deleted in colon cancer), DPC4 (deleted in pancreatic cancer), and MADR2 (mad related gene 2). The goals of the application are: to establish the smallest region of loss on 18q in oral SCC, to test the hypothesis that one or more TSGs within the smallest region of loss on 18q is associated with tumor progression; to test the hypothesis that restoration of the affected TSG will affect tumor growth or invasive behavior; and using markers identified in Aim 1 and the tissue specimens from a large, controlled, randomized treatment trial for SCC, test the hypothesis that 18q LOH is associated with survival and/or response to therapy. From these studies, the Principal Investigator expects to further define chromosome 18q alterations as an important feature of biologically advanced disease and to develop the knowledge for designing new strategies to counter the effect of tumor suppressor gene inactivation.

口腔鳞状细胞癌(SCC)是一种毁灭性和致命性疾病。 疾病。目前，几乎没有明确的指标来预测 肿瘤状态以外的其他临床处理的结果和决定 和淋巴受累。过去二十年的研究表明 表明基因缺陷是癌症发生和发展的基础，而且 在定义自然历史和生物学方面发挥关键作用 癌症的行为。首席调查员已经表明，损失 影响18号染色体长臂(18q)发生在55%-60%的 口腔鳞癌。初步数据表明，18q损失与 头颈部鳞状细胞癌预后差，死于癌症。此外， 18q上杂合性缺失(LOH)与骨髓瘤的进展相关 个别病人。如果首席调查员能够确定 这些发现的基础上，那么遗传标记就可以用于 选择高危患者进行更积极的治疗，并保留低风险患者 使患者面临不必要的治疗发病率风险。染色体区域 经常受到LOH影响的人被认为表明存在 肿瘤抑制基因(TSG)位于受累区域。三位候选人 在18q；DCC(在结肠癌中缺失)、DPC4上发现了TSG (在胰腺癌中缺失)和MADR2(MAD相关基因2)。这个 应用程序的目标是：建立最小的损失区域 在口腔鳞状细胞癌的18q，以检验假设一个或多个TSG内 18q上最小的缺失区域与肿瘤进展有关； 检验受影响的TSG恢复将影响的假设 肿瘤生长或侵袭行为；以及使用AIM中确定的标记 1和来自大型、对照、随机的组织样本 鳞状细胞癌的治疗试验，检验18q杂合性缺失相关的假设 生存和/或对治疗的反应。从这些研究中， 首席研究员预计将进一步定义18q号染色体 作为生物进展性疾病的重要特征的改变 发展知识以设计新的战略来应对 抑癌基因失活的影响。