Genome Wide Discovery of Molecular Alterations in Salivary Gland Tumors

描述(申请人提供)：涎腺恶性肿瘤是一种罕见的、异质性的头颈部癌症。粘液表皮样癌和腺样囊性癌是最常见的肿瘤，其临床病程难以预测，并伴有局部失败和远处转移。根据某些病理特征，治疗以手术为主，辅以放射治疗。化疗的作用，包括靶向治疗，都是研究性质的。高级别涎癌的五年生存率约为40%。鉴于这些肿瘤的罕见和多样性，到目前为止还没有进行全面的基因分析。然而，需要新的临床方法和新的分子靶点对于涎腺恶性肿瘤患者的治疗发展至关重要。通过对高级别粘液表皮样癌和腺样囊性癌进行全基因组测序，该项目将为涎腺癌的治疗、诊断和预后干预寻找潜在的新途径。为了进行突变筛查，我们将使用全基因组测序技术对20例临床标记的高度恶性粘液表皮样癌和20例腺样囊性癌样本进行分析。所有突变都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。然后，将在血浆和唾液中查询已识别的点突变和重排，以确定它们作为生物标志物的作用。识别这些基因改变和生物标志物可能会为涎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.