Exploring the role of polyploidy in tumor progression

探索多倍体在肿瘤进展中的作用

基本信息

批准号：
9759913
负责人：
Rachel Leanne Newcomb
金额：
$ 4.5万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9759913
关键词：
Affect Apoptosis Biological Assay Breast Cancer Model Cancer Patient Cells Computational algorithm Cytokinesis Data Diploidy Disease Down-Regulation Doxycycline Engineering Event Evolution Frequencies Genetic Genome Stability Genomics Goals Growth Human Malignant - descriptor Malignant Neoplasms Mammary Neoplasms Mediating Modeling Mus Mutation Oncogenes Oncogenic Patients Ploidies Polyploidy Population Prevalence Primary Neoplasm Recurrence Recurrent tumor Residual state Resistance Resistance development Role Shapes Small Interfering RNA Statistical Data Interpretation Stress System Technology Testing Tetraploidy Transgenic Mice Withdrawal antitumor effect cancer genome clinically relevant cohort exome sequencing fitness in vitro Assay in vivo inhibitor/antagonist insight knock-down mouse model outcome forecast resistance mutation response targeted treatment therapy resistant tumor tumor growth tumor progression tumorigenesis whole genome

项目摘要

Recent genomic analysis of human cancer sequencing data estimates over one third of human tumors undergo whole-genome duplication events. While applications of sequencing technology have revealed the prevalence of polyploidy in human cancer, the functional implications of polyploidy in cancer remain poorly defined. I propose to experimentally assess the effects of polyploidy on tumor progression using a murine model of breast cancer tumorigenesis. First, I will determine how polyploidy affects primary tumor growth. I will then determine if polyploidy influences the genetic alterations selected for in primary tumors. Finally, I will assess the consequences of polyploidy with respect to disease recurrence. I hypothesize that polyploidy promotes tumor growth in the context of primary tumor formation and recurrence, while uniquely shaping the genetic alterations present in tumors. Understanding how whole-genome duplication events affect tumor progression will provide important insight into the functional implications of polyploidy in cancer, and will yield a better understanding of events that shape the cancer genome.

最近对人类癌症测序数据的基因组分析估计超过三分之一的人类癌症肿瘤经历全基因组复制事件。测序技术的应用揭示了人类癌症中多倍体的流行，其功能意义癌症中的多倍体仍不清楚。我建议通过实验评估其效果使用乳腺癌肿瘤发生的小鼠模型研究多倍体对肿瘤进展的影响。首先，我会确定多倍体如何影响原发性肿瘤生长。然后我将确定是否是多倍体影响原发性肿瘤中选择的遗传改变。最后我会评估一下多倍体对疾病复发的影响。我假设多倍体在原发性肿瘤形成和复发的情况下促进肿瘤生长，同时独特塑造肿瘤中存在的遗传改变。了解全基因组复制的原理影响肿瘤进展的事件将为了解其功能意义提供重要的见解癌症中的多倍体，并将更好地了解塑造癌症的事件基因组。