Title | Differential clonal evolution in oesophageal cancers in response to neo-adjuvant chemotherapy |
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Type | Journal article |
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Authors | Findlay, J.M., Castro-Giner, F., Makino, S., Rayner, E., Kartsonaki, C., Cross, W., Kovac, M., Ulahannan, D., Palles, C., Gillies, R.S., MacGregor, T.P. and Church, D. |
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Abstract | How chemotherapy affects carcinoma genomes is largely unknown. Here we report whole-exome and deep sequencing of 30 paired oesophageal adenocarcinomas sampled before and after neo-adjuvant chemotherapy. Most, but not all, good responders pass through genetic bottlenecks, a feature associated with higher mutation burden pre-treatment. Some poor responders pass through bottlenecks, but re-grow by the time of surgical resection, suggesting a missed therapeutic opportunity. Cancers often show major changes in driver mutation presence or frequency after treatment, owing to outgrowth persistence or loss of sub-clones, copy number changes, polyclonality and/or spatial genetic heterogeneity. Post-therapy mutation spectrum shifts are also common, particularly C>A and TT>CT changes in good responders or bottleneckers. Post-treatment samples may also acquire mutations in known cancer driver genes (for example, SF3B1, TAF1 and CCND2) that are absent from the paired pre-treatment sample. Neo-adjuvant chemotherapy can rapidly and profoundly affect the oesophageal adenocarcinoma genome. Monitoring molecular changes during treatment may be clinically useful. |
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Article number | 11111 |
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Journal | Nature Communications |
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Journal citation | 7 |
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ISSN | 2041-1723 |
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Year | 2016 |
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Publisher | Nature Publishing Group |
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Publisher's version | License CC BY 4.0 File Access Level Open (open metadata and files) |
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Digital Object Identifier (DOI) | https://doi.org/10.1038/ncomms11111 |
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Web address (URL) | http://www.nature.com/doifinder/10.1038/ncomms11111 |
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Publication dates |
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Published | 05 Apr 2016 |
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