“Focus on the Individual; The importance of chromosome-specific biology in generating aneuploidy patterns in cancer”

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• Dr Sarah McClelland from Barts Cancer Institute, Queen Mary University of London
• Monday 01 June 2020, 13:00-14:15
• ZOOM (live).

If you have a question about this talk, please contact Anna Toporska.

Please email anna.toporska@cruk.cam.ac.uk to receive a ZOOM registration link

The genomes of cancer cells are highly abnormal, displaying aberrations at multiple scales ranging from single bases to copy number alterations (CNAs) affecting whole chromosomes (aneuploidy). Cancer genomes continually evolve over each of these scales, powered both by evolutionary selection and high rates of genetic instability including chromosomal instability (CIN). This ‘slippery characteristic’ of cancer cells likely allows tumours to develop resistance to therapy, therefore understanding the mechanisms that contribute to chromosomal instability is of key importance. A long-standing enigma of cancer genomes is the presence of recurrent patterns of aneuploidy. Since we know little about the selective pressures OR mutation rates of chromosomes, teasing apart the aetiology and importance of these recurrent patterns has not been possible to date. McClelland lab focusses on understanding the processes that generate aneuploidy in cancer (Burrell and McClelland et al, Nature 20131; Tamura et al, BioRXiv 20192) and they recently discovered that individual chromosomes behave differently during cell division and can thus become aneuploid or develop CNAs at different rates (Worrall et al, 20173; Tovini and McClelland, 20194; Shaikh et al, BioRXiv 20195). Moreover the specific mechanism generating aneuploidy, for example defects in mitosis, or aberrant DNA replication, generates a specific aneuploidy landscape3,5. Dr McClelland will present the findings they have made from modelling multiple different CIN mechanisms in diploid cells, and also from examining mechanisms and non-random aneuploidy in cancer cell models. She will also discuss the implications and applications of these findings to interpreting the origins and vulnerabilities of chromosomal instability in cancer.

This talk is part of the Seminars on Quantitative Biology @ CRUK Cambridge Institute series.

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