Molecular Classification of High Grade Endometrial Cancers: Extending TCGA Findings to a Diverse Population

高级别子宫内膜癌的分子分类：将 TCGA 研究结果扩展到不同人群

基本信息

批准号：
9269530
负责人：
Michele L. Cote
金额：
$ 61.87万
依托单位：
WAYNE STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-04 至 2021-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9269530
关键词：
Address Adjuvant Therapy Affect African American Area Automobile Driving Bioinformatics Biological Carcinoma Cessation of life Classification Clear Cell Clinical Clinical Data Comorbidity DNA Sequence Alteration Data Diagnosis Endometrial Carcinoma Endometrial Neoplasms Endometrioid Tumor Estrogens Ethnic group Exposure to Female Frequencies Gene Expression Gene Expression Profiling Histologic Histology Hormonal Hospitals Hysterectomy Incidence Knowledge Malignant Female Reproductive System Neoplasm Malignant Neoplasms Medical Records Michigan Microsatellite Instability Modeling Molecular Molecular Analysis Molecular Profiling Mutation Operative Surgical Procedures Pathologic Performance Population Population Heterogeneity Prevalence Progestins Progression-Free Survivals Public Health Race Research Sampling Serous Somatic Mutation Survival Analysis System The Cancer Genome Atlas Tissue-Specific Gene Expression Tumor Biology Tumor Tissue United States Variant Woman Work aged base cancer cell cancer diagnosis cancer survival clinically relevant exome sequencing genomic variation high risk hormone related cancer improved improved outcome novel outcome forecast personalized medicine public health relevance racial disparity study population transcriptome sequencing tumor

项目摘要

DESCRIPTION (provided by applicant): Endometrial cancer is the most common gynecological cancer and incidence is increasing in the United States. It also has one of the largest survival disparities of all common cancers, with approximately 20% fewer African American women surviving 5 years after diagnosis compared to white women, and this disparity holds across stages and histologic subtypes. Here we seek to examine a particularly aggressive subtype of endometrial cancers, high grade tumors including endometrioid, serous, clear cell and mixed carcinomas. These cancers are responsible for a disproportionate number of deaths from endometrial cancer, and are also more frequently diagnosed in African Americans. Specifically, we aim to: 1. Assess progression free survival and endometrial cancer-related survival in 500 women (250 African American, 250 white) diagnosed with high grade endometrial cancers, as defined by current pathologic standards; 2. Molecularly characterize (through whole exome sequencing and gene expression analysis) tumors from these women who received surgical treatment at two large research hospitals in Detroit, Michigan. We will perform integrated analysis to classify the tumors into biologically and clinically relevant groups and 3. Analyze the performance of the molecular classifications with respect to progression free survival and endometrial cancer- related survival, adjusting for relevant demographic, clinical, co-morbidity and treatment information. Preliminary work in this area has been done by The Cancer Genome Atlas (TCGA), but the tumors included were primarily from white women, with only 10 endometrioid and 11 serous tumors from African American women used to inform the molecular reclassification analysis. Thus, our project will address a large gap in current knowledge. Public Health Significance: The identification of novel somatic mutations and understanding of the spectrum of molecular variation, particularly among African Americans, will help us move further toward personalized medicine, with the potential to reduce the racial disparities in endometrial cancer survival and ultimately improve survival for all women with endometrial cancer.

描述（由申请人提供）：子宫内膜癌是最常见的妇科癌症，在美国其发病率正在上升，也是所有常见癌症中生存差异最大的癌症之一，非洲裔美国女性 5 年后的生存率减少了约 20%。与白人女性相比，这种差异存在于不同的阶段和组织学亚型中，在这里我们试图检查一种特别侵袭性的子宫内膜癌亚型，包括子宫内膜样癌、浆液性癌、子宫内膜癌等高级别肿瘤。这些癌症导致子宫内膜癌死亡人数不成比例，并且在非裔美国人中也更常见。具体而言，我们的目标是： 1. 评估 500 名患者的无进展生存期和子宫内膜癌相关生存期。根据现行病理标准，诊断出患有高级别子宫内膜癌的女性（250 名非裔美国人，250 名白人）2. 对这些女性的肿瘤进行分子特征分析（通过全外显子组测序和基因表达分析）；在密歇根州底特律的两家大型研究医院接受手术治疗的患者，我们将进行综合分析，将肿瘤分为相关的生物学和临床组，以及 3. 分析分子分类在无进展生存期和子宫内膜癌相关方面的表现。癌症基因组图谱 (TCGA) 已完成该领域的初步工作，但纳入的肿瘤主要来自白人女性，仅有 10 个子宫内膜样肿瘤和 10 个子宫内膜样肿瘤。 11 个来自非裔美国女性的浆液性肿瘤用于为分子重新分类分析提供信息，因此，我们的项目将解决当前公共卫生知识中的巨大差距：识别新的体细胞突变并了解分子变异谱，特别是在非洲。美国人将帮助我们进一步走向个性化医疗，有可能减少子宫内膜癌生存率的种族差异，并最终提高所有患有子宫内膜癌的女性的生存率。