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: 7204134
• 负责人: Norma Jean Nowak
• 金额: $ 29.29万
• 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/7204134
• 关键词: Allelic Imbalance; Biological Assay; Biological Markers; Carcinoma; Carcinoma in Situ; Cells; Cervical; Cervical lymph node group; Colon Carcinoma; DNA; Detection; Development; Diagnosis; Disease; Disease Progression; Distant Metastasis; Dysplasia; Early Diagnosis; Effectiveness; Epithelial; Epithelium; Event; Fluorescent in Situ Hybridization; Formalin; Gene Expression; Gene Expression Alteration; Genes; Genetic; Genome; Genomics; Goals; Head and Neck Squamous Cell Carcinoma; Histologic; Human Papillomavirus; Hybridization Array; Hyperplasia; Invasive; Knowledge; Larynx; Lead; Lesion; Leukoplakia; Loss of Heterozygosity; Malignant Neoplasms; Measures; Medical Surveillance; Monitor; Mouth Diseases; Mutation; Neoplasm Metastasis; Neoplasms; Normal tissue morphology; Numbers; Oligonucleotides; Oral; Oral Leukoplakia; Oral cavity; Paraffin; Paraffin Embedding; Patients; Pharyngeal structure; Population; Precancerous Conditions; Primary Neoplasm; Rate; Recurrence; Recurrent disease; Reporting; Resolution; Sampling; Series; Site; Staging; Surveys; Technology; Therapeutic Intervention; Tissues; Tobacco; Tumor Tissue; base; cancer genetics; comparative genomic hybridization; driving force; genome-wide analysis; lymph nodes; mortality; tumor; tumorigenesis

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）：每年报告大约 500,000 例头颈鳞状细胞癌 (HNSCC) 新病例，包括口腔、咽和喉。存在令人信服的证据表明 HNSCC 的不典型增生癌序列，其中需要一系列基因“打击”才能使细胞经历增生、不典型增生、原位癌、侵袭性肿瘤和转移性肿瘤。遗传不稳定性是大多数上皮癌（HNSCC）的必要条件。与结肠癌等其他形式的上皮肿瘤类似，通过杂合性丧失（等位基因失衡）衡量的遗传不稳定性是呼吸消化道内壁上皮的早期致癌事件，并且可能是克隆群体出现的关键驱动力。识别和检测肿瘤发生过程中呼吸消化道上皮内层发生的遗传事件进展的能力对于制定治疗干预策略至关重要。我们建议使用发现驱动的方法对口腔发育不良和 HNSCC 进行全面的全基因组分析，以努力识别和验证这些遗传事件。我们将检查前驱病变或不典型增生（表型为口腔白斑）、早期疾病（原发肿瘤，无颈部淋巴结转移）和晚期（原发肿瘤和颈部淋巴结转移，有/无远处转移）的病例进行基因组拷贝使用基于 BAC 阵列的比较基因组杂交 (aCGH) 进行数量变化。我们开发了这种方法并证明了其在识别拷贝数变化方面的有效性。我们的目的是确定一组生物标志物，以基因组拷贝数畸变的形式观察，可用于早期疾病检测和复发性疾病监测。显然，该分析还将有助于更好地了解导致侵袭性 HNSCC 的遗传事件。