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: 6176675
• 负责人: THOMAS E. CAREY
• 金额: $ 29.95万
• 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/6176675
• 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的 疾病 目前，几乎没有确切的指标可以预测 结果和确定除肿瘤状态以外的临床管理 和淋巴结受累。 过去二十年的研究 表明基因缺陷是癌症发展和进展的基础， 在定义自然历史和生物学方面发挥着关键作用 癌症的行为。 首席调查员表示， 影响18号染色体长臂（18 q）的发生在55- 60%的 口腔鳞状细胞癌初步数据表明，18 q丢失与 头颈部鳞状细胞癌预后差和死于癌症。此外，委员会认为， 18 q上的杂合性丢失（洛）与以下疾病的进展相关： 个别患者。 如果主要研究者能够识别 这些发现的基础上，那么遗传标记可以用于 选择高风险患者进行更积极的治疗， 使患者面临不必要的治疗并发症的风险。 染色体区域 经常受洛缺失影响的基因被认为表明存在一种 肿瘤抑制基因（TSG）在受影响的区域。 三个候选 TSG已在18 q上鉴定; DCC（在结肠癌中缺失），DPC 4 （在胰腺癌中缺失）和MADR 2（mad相关基因2）。 的 该应用程序的目标是：建立最小的损失区域 在口腔SCC的18 q上，以检验一个或多个TSG内 18 q上最小的丢失区域与肿瘤进展相关; 为了检验假设，即恢复受影响的TSG将影响 肿瘤生长或侵袭行为;并使用Aim中鉴定的标志物 1和来自大型、对照、随机 SCC的治疗试验，检验18 q洛与SCC的发生相关的假设。 生存率和/或对治疗的反应。 根据这些研究， 主要研究者希望进一步定义染色体18 q 改变作为生物学晚期疾病的重要特征， 发展设计新战略的知识， 肿瘤抑制基因失活的影响。