Tumor suppressor gene at 6q in adenoid cystic carcinoma

腺样囊性癌 6q 抑癌基因

• 批准号: 6611423
• 负责人: Christopher A. Moskaluk
• 金额: $ 33.3万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6611423
• 关键词: apoptosis; carcinogenesis; carcinoma; cell cycle; cell line; chromosomes; clinical research; extracellular matrix; fluorescent in situ hybridization; gene deletion mutation; gene expression; genetic mapping; human tissue; immunocytochemistry; laboratory mouse; neoplasm /cancer genetics; polymerase chain reaction; salivary gland neoplasms; tumor suppressor genes

DESCRIPTION (provided by applicant): Adenoid cystic carcinoma (ACC)is among the most common malignancies to arise in salivary glands, but little is known of the molecular mechanisms responsible for this disease. Prior and preliminary studies have identified the long arm of chromosome 6 (6q) as an area frequently deleted in ACC. Common deletion events are markers of known tumor suppressor genes in other cancers and the goal of this project is to test the hypothesis that a novel tumor suppressor gene exists on 6q which is responsible for ACC tumorigenesis. The Specific Aims are to 1) provide a more definitive genetic map of the common ACC deletion area on 6q in order to narrow the number of candidate genes that will have to be screened, 2) assay candidate genes for genetic characteristics of tumor suppressor genes and 3) assay candidate genes for functional characteristics of tumor suppressor genes. The cell line ACC3, derived from an adenoid cystic carcinoma, has been found to have a 6q deletion, and in support of these Aims, the deletion event in this cell line will be better characterized. Chromosomal transfer experiments will be performed to determine if ACC3 can serve as a model system to test for functional tumor suppression by genetic material on the 6q locus. Resources available to achieve these goals and carry out these Aims include an existing collection of primary ACC tumor samples, an established ACC tumor registry, a salivary gland tumor tissue microarray and oligonucleotide microarray gene expression data on a set of AGO and normal salivary gland tissue. There is no effective therapy for ACC, which is surgically non-resectable. Since there is an incomplete understanding of the molecular pathogenesis of ACC, there is little basis on which to rationally design and/or test new therapies. This application will address this deficiency. Since chromosome 6q deletions are common in other malignancies (breast cancer, ovarian cancer, melanoma) this knowledge may be generalizable to a larger population. Since AGO appears to have a smaller number of genetic changes than these other malignancies, it may serve as a simpler system to identify the 6q tumor suppressor gene.

描述（申请人提供）：腺样囊性癌（ACC）是涎腺最常见的恶性肿瘤之一，但对这种疾病的分子机制知之甚少。先前和初步的研究已经确定6号染色体长臂（6 q）是ACC中经常缺失的区域。常见的缺失事件是其他癌症中已知的肿瘤抑制基因的标记，本项目的目标是测试假设，即在6 q上存在一种新的肿瘤抑制基因，该基因负责ACC肿瘤的发生。具体目的是：1）提供6 q上常见ACC缺失区的更明确的遗传图谱，以缩小必须筛选的候选基因的数量，2）测定候选基因的肿瘤抑制基因的遗传特征，3）测定候选基因的肿瘤抑制基因的功能特征。已经发现源自腺样囊性癌的细胞系ACC 3具有6 q缺失，并且为了支持这些目的，将更好地表征该细胞系中的缺失事件。将进行染色体转移实验，以确定ACC 3是否可以作为模型系统，以测试6 q基因座上遗传物质的功能性肿瘤抑制。可用于实现这些目标和实现这些目标的资源包括现有的原发性ACC肿瘤样品的收集、已建立的ACC肿瘤登记处、唾液腺肿瘤组织微阵列和关于一组AGO和正常唾液腺组织的寡核苷酸微阵列基因表达数据。 目前尚无有效的治疗ACC的方法，手术不能切除ACC。由于对ACC的分子发病机制的理解不完全，因此几乎没有合理设计和/或测试新疗法的基础。本申请将解决这一缺陷。由于染色体6 q缺失在其他恶性肿瘤（乳腺癌，卵巢癌，黑色素瘤）中很常见，因此这一知识可能适用于更大的人群。由于AGO似乎比其他恶性肿瘤具有更少的遗传变化，因此它可以作为鉴定6 q肿瘤抑制基因的更简单的系统。