Whole genome array CGH of progressing oral dysplasia

进行性口腔发育不良的全基因组阵列 CGH

• 批准号: 7053364
• 负责人: WAN L LAM
• 金额: $ 26.37万
• 依托单位: BRITISH COLUMBIA CANCER AGENCY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7053364
• 关键词: bioinformatics; cancer information system; cell transformation; clinical research; fluorescent in situ hybridization; genetic markers; genome; human tissue; microarray technology; mouth neoplasms; neoplastic growth; neoplastic process; squamous cell carcinoma

DESCRIPTION (provided by applicant): Oral cancer represents a significant portion of head and neck cancer. The mortality rate for oral cancers is high, largely due to the late stage of diagnosis. Prognosis is better for patients detected early, preferably in the premalignant stage. Unfortunately, it is difficult to predict the risk of progression for the earliest stages (i.e., low-grade dysplasias) based on clinical and histological appearance. The objective of the proposed study is to use genomics to discover novel genetic markers to differentiate progressing low-grade dysplastic lesions from morphologically indistinguishable non-progressing low-grade lesions. The unique combination of clinical resources and genomics capacity in Vancouver enables the implementation of such a search for predictive markers. A centralized Oral Biopsy Service in British Columbia provides archival specimens with known outcome to support a retrospective identification of genetic alterations for use as candidate markers. A newly developed whole genome bacterial artificial chromosome array (uniquely containing the human genome in greater than 32,000 DNA segments) facilitates genome-wide profiling of minute specimens. Finally, an ongoing prospective study monitoring patients with low-grade dysplasia provides the infrastructure for validation of new genetic markers for progression. We will first use archival material to identify recurrent alterations in high-grade oral premalignant lesions (OPL) and tumors and select those that are frequent in progressing low-grade lesions but infrequent (or absent) in non-progressing lesions. Stepwise bioinformatics analysis will identify candidate progression markers from these alterations. The ability of these selected markers to predict disease outcome will then be tested in biopsies and exfoliated cell samples prospectively collected in the ongoing NIDCR-funded British Columbia Oral Cancer Prediction Longitudinal (OCPL) study. This information will be translated to new genetic tools, including a miniaturized OPL genomic DNA array and diagnostic FISH probes, which are optimized for analyzing minute lesion biopsies and exfoliated cells from lesion brushings. These tools will guide clinicians in the detection and management of early oral premalignant lesions.

描述（申请人提供）：口腔癌是头颈癌的重要组成部分。口腔癌的死亡率很高，主要是由于诊断较晚。早期发现的患者预后较好，最好是在癌前阶段。不幸的是，基于临床和组织学表现，很难预测早期阶段（即低级别发育不良）的进展风险。该研究的目的是利用基因组学发现新的遗传标记来区分进展性低级别发育不良病变和形态学上难以区分的非进展性低级别病变。