Biomarkers for the Progression of Head and Neck Squamous Cell Carcinoma

头颈鳞状细胞癌进展的生物标志物

• 批准号: 7031905
• 负责人: Norma Jean Nowak
• 金额: $ 29.79万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7031905
• 关键词: biomarker; clinical research; gene expression; genetics; head; lymph nodes; metastasis; neck; neoplasm /cancer; squamous cell carcinoma; tissues

DESCRIPTION (provided by applicant): Approximately 500,000 new cases of head and neck squamous cell carcinoma (HNSCC), including the oral cavity, pharynx and larynx, are reported each year. Compelling evidence exists for a dysplasia carcinoma sequence for HNSCC whereby a series of genetic 'hits' are required to allow cells to progress through hyperplasia, dysplasia, carcinoma in situ, invasive tumor, and metastatic tumor. Genetic instability is the sine qua non of most epithelial cancers with HNSCC following form. Similar to other forms of epithelial neoplasia such as colon cancer, genetic instability measured by loss of heterozygosity (allelic imbalance) is an early carcinogenic event in the epithelium lining the aerodigestive tract, and may be a key driving force in the emergence of clonal populations. The ability to recognize and detect the progression of genetic events occurring in the epithelium lining of the aerodigestive tract during tumorigenesis is critical to developing strategies for therapeutic intervention. We propose to use a discovery-driven approach to perform a comprehensive, genome-wide analysis of dysplasia of the oral cavity and HNSCC in our effort to identify and validate these genetic events. We will examine cases of precursor lesions or dysplasia (phenotypically observed as oral leukoplakia), early stage disease (primary tumor, no cervical lymph node metastases) and late stage (primary tumor and cervical lymph node metastases with/without distant metastases) for genomic copy number changes using BAC array based Comparative Genomic Hybridization (aCGH). We have developed this approach and demonstrated its effectiveness in identifying copy number changes. Our intent is to identify a set of biomarkers, observed as genomic copy number aberrations, that can be used for early disease detection and monitoring for recurrent disease. Clearly, the analysis will also lead to a better understanding of the genetic events leading to invasive HNSCC.

描述（由申请人提供）：每年都有大约500,000例头颈部鳞状细胞癌（HNSCC）的新病例，包括口腔，咽部和larynx。对于HNSCC的发育不良癌序列存在令人信服的证据，因此，需要一系列遗传“命中”，以使细胞通过增生，发育异常，原位癌，侵入性肿瘤和转移性肿瘤发展。遗传不稳定性是大多数具有HNSCC以下形式的上皮癌的正弦物质。与其他形式的上皮肿瘤（如结肠癌）相似，通过杂合性丧失（等位基因失衡）测得的遗传不稳定性是衬砌气管种群的上皮层中的早期致癌事件，并且可能是克隆种群出现的关键驱动力。在肿瘤发生过程中，识别和检测在气化道的上皮衬里中发生的遗传事件的进展对于制定治疗干预策略至关重要。我们建议使用以发现驱动的方法对口腔和HNSCC进行全面的全基因组发育不良进行全面的，全基因组的分析，以识别和验证这些遗传事件。 We will examine cases of precursor lesions or dysplasia (phenotypically observed as oral leukoplakia), early stage disease (primary tumor, no cervical lymph node metastases) and late stage (primary tumor and cervical lymph node metastases with/without distant metastases) for genomic copy number changes using BAC array based Comparative Genomic Hybridization (aCGH).我们已经开发了这种方法，并证明了其在识别拷贝数更改方面的有效性。我们的目的是识别一组被视为基因组拷贝数畸变的生物标志物，可用于早期疾病检测和监测复发性疾病。显然，该分析还将更好地理解导致侵入性HNSCC的遗传事件。