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 肿瘤经历全基因组复制事件。而测序技术的应用 揭示了多倍体在人类癌症中的流行，以及多倍体基因的功能含义 癌症中的多倍体仍然没有明确的定义。我建议从实验上评估 利用乳腺癌发生的小鼠模型进行肿瘤进展的多倍体研究。首先，我会 确定多倍体如何影响原发肿瘤的生长。然后我会确定多倍体是否 影响原发肿瘤中选择的基因改变。最后，我将评估 多倍体对疾病复发的影响。我假设多倍体 在原发肿瘤形成和复发的背景下促进肿瘤生长，而独特的 塑造肿瘤中存在的基因改变。了解全基因组复制是如何 影响肿瘤进展的事件将为深入了解血管紧张素转换酶的功能 多倍体在癌症中的作用，并将使人们更好地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.