报告题目：Mitotic error can generate chromothripsis and other complex 

          chromosomal rearrangements

报告人：美国Broad Institute Dr. Cheng-Zhong Zhang

        Computational Biologist,

        Broad institute of Harvard and MIT

        Supervisor: Matthew L. Meyerson, M.D., Ph.D.

时间：2014年10月16日上午10：00

地点：北京大学综合科研楼302会议室

联系人：白凡（62756164）

Recent genome sequencing has uncovered a new mutational outcome in cancer and human congenital disorders called chromothripsis. Chromothripsis is characterized by extensive chromosome rearrangements and an oscillating pattern of DNA copy number alterations, all mysteriously restricted to one or a few chromosomes. The mechanism for chromothripsis is unknown, but we previously proposed it might occur through the physical isolation of chromosomes in aberrant nuclear structures called micronuclei. Here we combined live-cell imaging and single-cell genome sequencing to test this idea. These experiments demonstrate that micronucleation can indeed cause a wide range of structural rearrangements of chromosomes, which in some cases recapitulate all the hallmark features of chromothripsis. We report direct evidence that the mechanism for chromothripsis can involve the fragmentation of a single chromatid in a micronucleus within a single cell division cycle. Additionally, we detect sequence signatures consistent with DNA replication template-switching, an error that has also been implicated in chromothripsis. Together, these experiments define a new human disease-relevant mutational process of which chromothripsis is one extreme outcome.