Exploring the role of polyploidy in tumor progression

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患者的基因组中， 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， 癌症中的多倍性仍然不清楚。我建议通过实验来评估 使用乳腺癌肿瘤发生的鼠模型，研究了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。然后我将确定多倍体 影响原发性肿瘤中选择的遗传改变。最后，我将评估 多倍体的后果与疾病复发有关。我假设多倍性 在原发性肿瘤形成和复发的背景下促进肿瘤生长，同时独特地 形成肿瘤中存在的遗传改变。了解全基因组复制 影响肿瘤进展的事件将提供重要的洞察力， 癌症中的多倍性，并将产生更好的理解形成癌症的事件 基因组

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.