Wednesday, September 15, 2021

CCMB Seminar: "A pancancer compendium of chromosomal instability"

4:00 PM

Forum Hall, 4th Floor, Palmer Commons Building

Hosted by Josh Welch

CCMB Seminar Series – sponsored by DCMB
by Dr. Florian Markowetz (Senior Group Leader; Royal Society Wolfson Research Merit)

Abstract

Chromosomal instability (CIN) results in the accumulation of large-scale losses, gains, and rearrangements of DNA. The broad genomic complexity caused by CIN is a hallmark of cancer, however, there is no systematic framework to measure different types of CIN and their impact on clinical phenotypes. Here, we evaluate the extent, diversity and origin of chromosomal instability across 7,880 tumours representing 33 cancer types from the TCGA collection. We present a compendium of 17 copy number signatures characterising specific types of CIN, with putative aetiologies supported by multiple independent data sources. The signatures predict drug response and identify new drug targets. Our framework refines the understanding of impaired homologous recombination, one of the most therapeutically targetable types of CIN. Our results illuminate a fundamental structure underlying genomic complexity and provide a resource to guide future CIN research in human cancers.

Bio

Florian Markowetz is a Senior Group Leader at the Cancer Research UK Cambridge Institute. He is a Royal Society Wolfson Research Merit Award holder and received a CRUK Future Leader in Cancer Research prize. He holds degrees in Mathematics (Dipl. math.) and Philosophy (M.A.) from the University of Heidelberg and a Dr. rer. nat. (PhD equivalent) in Computational Biology from Free University Berlin, for which he was awarded an Otto-Hahn Medal by the Max Planck Society. His group at the CRUK Cambridge Institute combines computational work on cancer evolution and image analysis of the tumour tissue with experimental work on understanding key cancer mechanisms like the estrogen receptor.