Genome Wide Discovery of Molecular Alterations in Salivary Gland Tumors

描述（申请人提供）：唾液腺恶性肿瘤是罕见和异质性的头颈部癌症。粘液表皮样和腺样囊性癌是最常见的，表现出不可预测的临床过程，局部失败和远处转移。治疗主要是手术，然后根据某些病理特征进行辅助放疗。化疗的作用，包括靶向治疗，是研究性的。高级别唾液癌的5年生存率约为40%。鉴于这些肿瘤的罕见性和多样性，迄今为止尚未进行全面的遗传分析。然而，需要新的临床方法和新的分子靶点对涎腺恶性肿瘤患者的治疗发展至关重要。通过对高级别黏液表皮样和腺样囊性癌进行全基因组测序，该项目将为唾液腺癌的治疗、诊断和预后干预找到潜在的新途径。为了进行突变筛选，我们将对临床注释的20例高级别粘液表皮样癌和20例腺样囊性癌样本进行全基因组测序。所有突变将在同一患者的正常DNA中进行检查，以识别和确认体细胞突变和重排。鉴定出的点突变和重排将在血浆和唾液中进行查询，以确定它们作为生物标志物的作用。这些基因改变和生物标志物的鉴定将可能为唾液腺恶性肿瘤提供潜在的预后、诊断和治疗策略。

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.