The Department of Human Molecular Genetics and Biochemistry cordially invites you to a special seminar

LECTURER

Dr. Ofer Shosani

Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine,

University of California, San Diego, USA

“Order from chaos: Chromosome Catastrophes Drive Cancer Evolution”

Abstract: 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 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. Second, 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. I will conclude by discussing an outlook towards the exciting new directions opened by this work.

The seminar will take place on Tuesday, December 1st, at 10:00 AM, via zoom

Join Zoom Meeting

https://us02web.zoom.us/j/83645287656

Meeting ID: 836 4528 7656