Epigenomic Markers of HNSCC Survival Across Ethnic Groups

各族裔 HNSCC 存活的表观基因组标记

基本信息

批准号：
8922403
负责人：
Rafael Guerrero-Preston
金额：
$ 12.16万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-22 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8922403
关键词：
Address African American Bioinformatics Biological Biological Markers Blood Cells Case Series Case-Control Studies Cataloging Catalogs Chromosomal Duplication Chromosome Deletion Clinical Clinical Management Cohort Studies Communities DNA DNA Methylation Data Data Set Databases Diagnosis Disease-Free Survival Early Diagnosis Eastern Cooperative Oncology Group Epigenetic Process Ethnic group Funding Opportunities Genes Genetic Genomics Goals HOXA9 gene Head and Neck Cancer Head and Neck Squamous Cell Carcinoma Healthcare Systems High Prevalence Hypermethylation Latino Loss of Heterozygosity Malignant Neoplasms Malignant neoplasm of cervix uteri Mentored Research Scientist Development Award Mentorship Methylation Mission Mutation National Cancer Institute Ontology Operative Surgical Procedures Oral Oral cavity Oral mucous membrane structure Otolaryngology Outcome Pathogenesis Pathway interactions Patients Pharyngeal structure Postoperative Period Prevalence Primary carcinoma of the liver cells Puerto Rican Puerto Rico Race Radiation Therapy Oncology Group Recurrence Relative (related person)Research Design Research Personnel Risk Saliva Salivary Sampling Smoking Solid Specimen Staging Surgical margins Survival Rate TP53 gene Testing Time Tissue Sample Tissues Training Tumor Tissue United States anticancer research base cancer health disparity cohort epigenomics follow-up genome-wide improved instructor male malignant mouth neoplasm malignant oropharynx neoplasm medical schools men mortality novel outcome forecast promoter repository research facility response tumor

项目摘要

Project Summary This is a K01 application submitted by Dr. Rafael Guerrero-Preston in response to the funding opportunity announcement "NCI Mentored Research Scientist Development Award to Promote Diversity (K01)" - PAR-09- 052. Rafael, born and raised in Puerto Rico, is currently appointed as an Instructor at the Head and Neck Cancer Research Division of the Department of Otolaryngology at Johns Hopkins School of Medicine. Rafael's short term goals are to examine global, genome-wide and gene-specific epigenomic alterations in tumors that disproportionally burden African American and Latino communities: hepatocellular carcinoma, cervical cancer and head and neck cancers. Dr Guerrero-Preston's long-term goals are: to develop epigenomic biomarkers to improve Head and Neck Cancer (HNSCC) early detection and clinical management; and to contribute to the reduction of survival disparities in oral and oropharyngeal cancer. The proposed K01 project addresses two objectives relevant to the National Cancer Institute mission: to train culturally diverse cancer researchers; and to eliminate cancer health disparities. The overall HNSCC survival rates for African American patients in the United States has remained close to 20% higher than Whites for more than 30 years, but the biological basis for this disparity is poorly understood. A two-stage epigenomic study design is proposed to test the hypothesis that epigenetic alterations contribute to ethnic disparities in HNSCC survival by examining the following aims: Specific Aim 1: a) To assess differences of global DNA methylation across ethnic groups in tumor-surgical margins pairs of HNSCC patients (n=500); b) To quantify NID2 and HOXA9 differential methylation across ethnic groups in tumor-surgical margins pairs of HNSCC patients (n=500); c) To evaluate the association between differential methylation in tumor-surgical margin pairs, TP53 mutation status, and clinical outcome, including local recurrence and survival across ethnic groups. Specific Aim 2: a) To assess differences of global DNA methylation across ethnic groups in tumor tissue from HNSCC cases (n=300) and normal oral mucosa controls (n=300); b) To quantify NID2 and HOXA9 differential methylation across ethnic groups in tumor tissue from HNSCC cases (n=300) and normal oral mucosa controls (n=300); c) To evaluate the association between differential methylation in tissue and clinical outcome, including local recurrence and survival across ethnic groups. This K01 project strengths are multiple: mentorship by two world leaders in HNSCC genomics, David Sidransky and Wayne Koch; solid institutional support; use of world class research facilities in Johns Hopkins School of Medicine; and access to well characterized sample repositories - the ECOG E4393/RTOG 9614 study, a large multi-institutional head and neck cancer tumor-surgical margin study cohort with abundant outcome data; and a retrospective case-control study from samples stored by the Johns Hopkins Head and Neck Cancer SPORE

项目概要这是 Rafael Guerrero-Preston 博士针对资助机会提交的 K01 申请公告“NCI 指导研究科学家促进多样性发展奖 (K01)”- PAR-09- 052.拉斐尔，在波多黎各出生和长大，目前被任命为头颈教练约翰霍普金斯大学医学院耳鼻喉科癌症研究部。拉斐尔的短期目标是检查肿瘤中的全局、全基因组和基因特异性表观基因组改变，给非裔美国人和拉丁裔社区带来不成比例的负担：肝细胞癌、宫颈癌以及头颈癌。 Guerrero-Preston 博士的长期目标是：开发表观基因组生物标志物改善头颈癌（HNSCC）的早期检测和临床管理；并为减少口腔癌和口咽癌的生存差异。拟议的 K01 项目解决了两个问题与国家癌症研究所使命相关的目标：培训文化多元化的癌症研究人员；和消除癌症健康差异。非洲裔美国患者 HNSCC 的总体生存率美国30多年来一直比白人高出近20%，但生物学基础因为人们对这种差异知之甚少。提出了两阶段表观基因组研究设计来检验该假设通过检查以下目标，表观遗传改变会导致 HNSCC 生存的种族差异：具体目标 1：a) 评估肿瘤手术中不同种族群体的总体 DNA 甲基化差异 HNSCC 患者的边缘对 (n=500)； b) 量化 NID2 和 HOXA9 差异甲基化 HNSCC 患者肿瘤-手术切缘对中的种族群体 (n=500)； c) 评估关联肿瘤-手术切缘对的差异甲基化、TP53突变状态和临床结果之间，包括跨种族的局部复发和生存。具体目标 2：a) 评估来自不同种族群体的肿瘤组织中总体 DNA 甲基化的差异 HNSCC 病例 (n=300) 和正常口腔粘膜对照 (n=300)； b) 量化 NID2 和 HOXA9 差异 HNSCC 病例 (n=300) 和正常口腔粘膜对照的肿瘤组织中跨种族的甲基化 (n=300)； c) 评估组织中差异甲基化与临床结果之间的关联，包括跨种族的局部复发和生存。这个 K01 项目的优势是多方面的：由 HNSCC 基因组学领域的两位世界领袖 David 提供指导西德兰斯基和韦恩·科赫；坚实的制度支持；使用约翰·霍普金斯大学世界一流的研究设施医学院；并访问特征明确的样本存储库 - ECOG E4393/RTOG 9614 研究，一个大型多机构头颈癌肿瘤手术切缘研究队列，具有丰富的结果数据；以及对约翰·霍普金斯大学校长储存的样本进行的回顾性病例对照研究颈部癌孢子

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Phospho-ΔNp63α-dependent regulation of autophagic signaling through transcription and micro-RNA modulation.

通过转录和 micro-RNA 调制对自噬信号进行磷酸化-αNp63α 依赖性调节。

DOI：
发表时间：
2012-03-15
期刊：
影响因子：
0
作者：
Huang, Yiping;Guerrero;Ratovitski, Edward A
通讯作者：
Ratovitski, Edward A

Cold plasma selectivity and the possibility of a paradigm shift in cancer therapy.

冷等离子体选择性和癌症治疗范式转变的可能性。

DOI：
发表时间：
2011-10-25
期刊：
影响因子：
8.8
作者：
Keidar, M;Walk, R;Shashurin, A;Srinivasan, P;Sandler, A;Dasgupta, S;Ravi, R;Guerrero;Trink, B
通讯作者：
Trink, B

Prenatal exposure to tobacco smoke leads to increased mitochondrial DNA content in umbilical cord serum associated to reduced gestational age.

产前接触烟草烟雾会导致脐带血清中线粒体 DNA 含量增加，从而导致胎龄缩短。

DOI：
发表时间：
2017-02
期刊：
影响因子：
3.2
作者：
Pirini, Francesca;Goldman, Lynn R;Soudry, Ethan;Halden, Rolf U;Witter, Frank;Sidransky, David;Guerrero
通讯作者：
Guerrero

Genome-wide analysis of genetic alterations in testicular primary seminoma using high resolution single nucleotide polymorphism arrays.

使用高分辨率单核苷酸多态性阵列对睾丸原发性精原细胞瘤的遗传改变进行全基因组分析。

DOI：
发表时间：
2011-06
期刊：
影响因子：
4.4
作者：
LeBron, Cynthia;Pal, Prodipto;Brait, Mariana;Dasgupta, Santanu;Guerrero;Looijenga, Leendert H J;Kowalski, Jeanne;Netto, George;Hoque, Mohammad O
通讯作者：
Hoque, Mohammad O

INSIG2 rs7566605 single nucleotide variant and global DNA methylation index levels are associated with weight loss in a personalized weight reduction program.

INSIG2 rs7566605 单核苷酸变异和整体 DNA 甲基化指数水平与个性化减肥计划中的体重减轻相关。

DOI：
发表时间：
2018-01
期刊：
影响因子：
3.4
作者：
Pirini, Francesca;Rodriguez;Ayandibu, Bola Grace;Orera;Gonzalez;Lawson, Fahcina;Thorpe Jr, Roland J;Sidransky, David;Guerrero
通讯作者：
Guerrero