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.

报告时间：10月16日早上10：00    

报告地点：BIOPIC大会议室

报告内容：

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.

联系人：白凡研究员，56164