传统的癌症发生理论认为细胞的癌变是由基因突变的累积所引起。然而，最近在肿瘤细胞中发现了一种被称为“染色体粉碎”的现象，即细胞的一条或数条染色体裂解成几十甚至数百个碎片，之后大部分碎片又被随机地重新组装起来，从而在很短的时间内造成大量的染色体重排和基因突变，使正常细胞完成向癌细胞的转化。该现象被认为是一种癌基因组快速进化的途径，并可能揭示了一种肿瘤发生发展的新机制。目前对该现象的研究仅来自于有限的基于基因组数据的分析，“染色体粉碎及重组”是否确为细胞癌变的新机制以及其内在发生机制仍不清楚。本课题拟采用系统生物学的手段，设计算法整合多种高通量组学数据，包括基因组、转录组、表观基因组和体细胞突变等，研究染色体粉碎区域的特征，识别与染色体粉碎相关的基因及重要功能通路，并加以验证，探索其分子机制。本项目的研究结果将促进系统地理解癌基因组快速进化的途径，为阐明癌症发生发展的新机制提供理论依据。

According to the classic theory of tumorogenesis, cancer is caused by the accumulation of gene mutations. However, recently a phenomenon called “Chromothripsis” was found in cancer cells. In this event, one or several chromosomes in a cell are smashed into dozens or even hundreds of pieces. Then most of these pieces are randomly pieced together. It will cause huge numbers of chromosome rearrangements and gene mutations in a very short time, and will convert a normal cell to cancer cell. This phenomenon was considered as rapid evolution of cancer genome, and may represent a new mechanism in cancer initiation and development. At the moment, there are only limited studies that based on genome data analysis about this phenomenon. It is still unknown that whether chromothripsis and its rearrangement is a new mechanism in cancer development. And the mechanism is also unknown. This project is supposed to use systems biology methods, and design an algorithm to integrate multiple high throughput omits data, including genomics, transcriptomics, epigenomics, somatic mutation and so on. These data will be used to describe the characters of chromothripsis region, to identify the important genes and pathways in chromothripsis event. At last, we will confirm these results by experiments, and deduce its molecular mechanism. The results of this project will promote systematic understanding of the rapid evolution of cancer genome, provide the theoretical foundation of the new mechanism involved in cancer initiation and progression.