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: 6796963
• 负责人: WAN L LAM
• 金额: $ 27万
• 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/6796963
• 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（由申请人提供）：口腔癌是头颈癌的重要组成部分。口腔癌的死亡率很高，主要是由于诊断的晚期。早期发现的患者预后较好，最好是在癌前阶段。不幸的是，很难预测最早阶段的进展风险（即，低度发育不良）。这项研究的目的是利用基因组学发现新的遗传标记，以区分进行性低度异型增生病变与形态学上无法区分的非进行性低度病变。 温哥华的临床资源和基因组学能力的独特组合使得能够实施这样的预测标记物搜索。不列颠哥伦比亚省的一个集中的口腔活检服务提供了具有已知结果的档案标本，以支持作为候选标记物使用的遗传改变的回顾性鉴定。新开发的全基因组细菌人工染色体阵列（独特地包含超过32，000个DNA片段的人类基因组）有助于对微小标本进行全基因组分析。最后，一项正在进行的监测低度异型增生患者的前瞻性研究为验证新的进展遗传标志物提供了基础设施。我们将首先使用档案材料，以确定在高级别的口腔癌前病变（OPL）和肿瘤的复发性改变，并选择那些经常在进展性低级别病变，但不常见（或不存在）在非进展性病变。逐步生物信息学分析将从这些改变中鉴定候选进展标志物。这些选定的标志物预测疾病结果的能力将在活检和脱落细胞样本中进行测试，这些样本是在正在进行的NIDCR资助的不列颠哥伦比亚省口腔癌预测纵向（OCPL）研究中前瞻性收集的。这些信息将被转化为新的遗传工具，包括微型OPL基因组DNA阵列和诊断性FISH探针，这些探针经过优化，用于分析微小病变活检和病变刷拭的脱落细胞。这些工具将指导临床医生在早期口腔癌前病变的检测和管理。