演題：Chromothripsis and Genomic Instability from Mitotic Errors

演者：Dr. Peter Ly

(Assistant Professor, Children’s Research Institute 

 UT Southwestern Medical Center)

抄録：

Most cancer cells harbor complex genomes with numerical and structural chromosomal abnormalities. My laboratory investigates the mechanisms that shape the chaotic mutational landscape of cancer genomes. We are particularly interested in a class of complex genome rearrangements generated by the catastrophic shattering of individual chromosomes. This process – termed chromothripsis – is initiated by mitotic errors that entrap missegregated chromosomes within aberrant nuclear structures called micronuclei. DNA damage and DNA replication defects within micronuclei trigger shattering of the missegregated chromosome into tens to hundreds of fragments. Reassembly of these fragments by error-prone DNA repair pathways generates highly rearranged chromosomes with extensive DNA copy-number alterations. Chromothripsis exemplifies a rapid mutational process in which numerous genetic lesions can be acquired within a few cell cycles, ranging from the simultaneous inactivation of multiple tumor suppressor genes to the production of extrachromosomal DNA carrying amplified oncogenes. Our long-term goal is to understand how mitotic errors, micronuclei, and chromothripsis contribute to cancer genome instability, tumorigenesis, and resistance to anti-cancer therapeutics. In this seminar, I will present our latest findings on how chromothripsis arises and how mitotic errors can propagate genomic instability to neighboring cells.

Refs）"The Fanconi anemia pathway induces chromothripsis and ecDNA-driven cancer drug resistance” Engel et al., Cell 187:6055-6070 (2024), 

"Mitotic clustering of pulverized chromosomes from micronuclei” Lin et al., Nature 618:1041-1048 (2023)

日　時：2026年3月6日（金）16：00 〜 17 : 00

場　所：吉田記念講堂