Order from Chaos: Chromosome Catastrophes Drive Cancer Evolution
Date:
Lecture / Seminar
Time: 10:00-11:00
Location: Nella and Leon Benoziyo Building for Biological Sciences
Lecturer: Dr. Ofer Shoshani
Organizer: Department of Biomolecular Sciences
Details: Department of Cellular and Molecular Medicine, University of California, San Diego
Abstract: Chromosomal instability is one of the major hallmarks in cancer driving numerica ... Read more Chromosomal instability is one of the major hallmarks in cancer driving numerical and structural chromosome aberrations. Cancer cells can use the chaotic background of chromosome instability to generate ordered genomic events leading to accelerated tumor formation or drug resistance. First, I will discuss how transient centrosome amplification can induce a burst of chromosomal instability in vivo. This triggers the formation of random aneuploidies (changes in chromosome numbers) with cancer initiating cells carrying a specific aneuploidy signature leading to accelerated tumorigenesis. This work has uncovered aneuploidy as a direct driver of cancer and enables a better understanding of the involvement of specific aneuploidies in cancer. Second, I will describe how chromothripsis, the catastrophic shattering of a chromosome and random religation of its pieces, can promote resistance to therapy. Using cancer cells and patient samples, I identified that chromothripsis drives the formation and evolution of extrachromosomal DNA (ecDNA) elements that can amplify genes conferring drug resistance. Chromothripsis depends on non-homologous DNA end joining repair, a vulnerability that could be exploited for therapeutic purposes by preventing resistance to chemotherapy. I will conclude by discussing an outlook towards the exciting new directions opened by this work.
Close abstract
