Genome Wide Discovery of Molecular Alterations in Salivary Gland Tumors

唾液腺肿瘤分子改变的全基因组发现

基本信息

批准号：
8443710
负责人：
Nishant Agrawal
金额：
$ 24.3万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-03 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8443710
关键词：
Accounting Adenoid Cystic Carcinoma Adjuvant Radiotherapy Biological Assay Biological Markers Carcinoma Clinical Critical Pathways DNA DNA Sequence Rearrangement Development Diagnostic Distant Metastasis Failure Gene Rearrangement Genes Genomics Head and Neck Cancer Head and neck structure Human Incidence Intervention Liquid substance Malignant Neoplasms Malignant neoplasm of salivary gland Molecular Molecular Target Mucoepidermoid Carcinoma Mutate Mutation Operative Surgical Procedures Pathogenesis Pathologic Patients Plasma Point Mutation Role Saliva Salivary Salivary Gland Neoplasms Salivary Glands Sampling Screening procedure Somatic Mutation Therapeutic United States Validation Work base cancer genome chemotherapy digital genetic analysis genome sequencing genome-wide novel novel strategies prognostic therapy development tumor

项目摘要

DESCRIPTION (provided by applicant): Salivary gland malignancies are rare and heterogeneous cancers of the head and neck. Mucoepidermoid and adenoid cystic carcinoma are the most common and demonstrate an unpredictable clinical course with locoregional failure and distant metastasis. Treatment is primarily surgical followed by adjuvant radiotherapy based on certain pathologic features. The role of chemotherapy, including targeted therapy, is investigational. The five year survival for high grade salivary carcinomas is approximately 40%. Given the rarity and diversity of these tumors, comprehensive genetic analysis has not been performed to date. However, there is a need for novel clinical approaches and new molecular targets are critically important for therapy development in patients with salivary gland malignancies. By performing whole genome sequencing on high grade mucoepidermoid and adenoid cystic carcinoma, this project will identify potential new avenues for therapeutic, diagnostic and prognostic intervention in salivary gland cancer. For mutational screening, we will employ whole genome sequencing on clinically annotated 20 high grade mucoepidermoid carcinoma and 20 adenoid cystic carcinoma samples. All mutations will be examined in normal DNA from the same patient to identify and confirm somatic mutations and rearrangements. The point mutations and rearrangements that are identified will then be queried in the plasma and saliva to identify their roles as biomarkers. Identification of these genetic alterations and biomarkers will likely provide potential prognostic, diagnostic and therapeutic strategies for salivary gland malignancies. PUBLIC HEALTH RELEVANCE: We will perform whole genome sequencing on twenty high grade mucoepidermoid carcinomas and twenty adenoid cystic carcinomas. We will identify key genes and pathways critical to these tumor types. Based on these findings, we will develop and validate circulating tumor DNA as a biomarker in salivary gland malignancies.

描述（由申请人提供）：唾液腺恶性肿瘤是罕见的，并且头颈部异质性癌症。粘膜皮肤类药物和腺样性囊性癌是最常见的，并且表现出具有局部局部衰竭和远处转移的不可预测的临床过程。治疗主要是手术，然后是基于某些病理特征的辅助放疗。化学疗法的作用，包括靶向治疗，是研究的。高级唾液癌的五年生存率约为40％。鉴于这些肿瘤的稀有性和多样性，迄今为止尚未进行全面的遗传分析。但是，需要新颖的临床方法，而新的分子靶标对于唾液腺恶性肿瘤患者的治疗发展至关重要。通过对高级粘膜外皮样和腺样性囊性癌进行整个基因组测序，该项目将确定潜在的唾液腺癌治疗，诊断和预后干预的新途径。为了进行突变筛查，我们将在临床注释的20个高级粘膜表皮癌和20个腺样囊性癌癌样品上使用全基因组测序。所有突变将在同一患者的正常DNA中检查，以识别和确认体细胞突变和重排。然后，在血浆和唾液中查询确定的点突变和重排，以识别其作为生物标志物的作用。这些遗传改变和生物标志物的鉴定可能会为唾液腺恶性肿瘤提供潜在的预后，诊断和治疗策略。公共卫生相关性：我们将对二十种高级粘膜表皮癌和二十个腺样囊性癌进行整个基因组测序。我们将确定对这些肿瘤类型至关重要的关键基因和途径。根据这些发现，我们将开发并验证循环肿瘤DNA作为唾液腺恶性肿瘤中的生物标志物。