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: 6379828
• 负责人: THOMAS E. CAREY
• 金额: $ 30.85万
• 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/6379828
• 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) 是一种破坏性且致命的癌症 疾病。 目前，缺乏明确的预测指标 结果并确定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生和进展的基础，并且 在定义自然历史和生物学方面发挥着至关重要的作用 癌症的行为。 首席研究员表明，损失 影响 18 号染色体长臂 (18q) 的概率为 55-60% 口腔鳞状细胞癌。初步数据表明 18q 丢失与 头颈部鳞状细胞癌预后不良，甚至死于癌症。而且， 18q 杂合性丢失 (LOH) 与疾病进展相关 个别患者。 如果首席研究员能够识别 根据这些发现，遗传标记可用于 选择高风险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风险。 染色体区域 经常受 LOH 影响被认为表明存在 受影响区域内的肿瘤抑制基因（TSG）。 三位候选人 TSG 已在 18q 上被识别； DCC（结肠癌中缺失）、DPC4 （在胰腺癌中缺失）和 MADR2（mad 相关基因 2）。 这 应用程序的目标是：建立最小的损失区域 在口腔 SCC 的 18q 上，检验以下假设： 18q 上最小的缺失区域与肿瘤进展相关； 检验受影响 TSG 的恢复将影响的假设 肿瘤生长或侵袭行为；并使用 Aim 中识别的标记 1 组织样本来自大型、受控、随机 SCC 治疗试验，检验 18q LOH 相关的假设 与生存和/或对治疗的反应。 从这些研究中， 首席研究员期望进一步定义18q染色体 改变是生物学晚期疾病的一个重要特征 发展设计新战略来应对的知识 抑癌基因失活的影响。