Impact of mutational profiles on response of primary oestrogen receptor-positive breast cancers to oestrogen deprivation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-11-09

AUTHORS

Pascal Gellert, Corrinne V. Segal, Qiong Gao, Elena López-Knowles, Lesley-Ann Martin, Andrew Dodson, Tiandao Li, Christopher A. Miller, Charles Lu, Elaine R. Mardis, Alexa Gillman, James Morden, Manuela Graf, Kally Sidhu, Abigail Evans, Michael Shere, Christopher Holcombe, Stuart A. McIntosh, Nigel Bundred, Anthony Skene, William Maxwell, John Robertson, Judith M. Bliss, Ian Smith, Mitch Dowsett, Stephen Johnston, Radha Todd, Kieran Horgan, Stephen Chan, Simon D. H. Holt, Marina Parton, Ian Laidlaw, Jayant S. Vaidya, Tracey Irvine, Fiona Hoar, Ilyas Khattak, Ashutosh Kothari, Lucy Brazil, Nicholas Gallegos, Duncan Wheatley, Tayo Johnson, Geoffrey Sparrow, Serena Ledwidge, Caroline Mortimer, Marcus Ornstein, Douglas Ferguson, Douglas Adamson, Ramsey Cutress, Richard Johnson, Clare Crowley, Zoe Winters, Hisham Hamed, Russell Burcombe, Susan Cleator, Muireann Kelleher, Jonathan Roberts, Sarah Vesty, Maher Hadaki, Mary Quigley, Julie Doughty, Siobhan Laws, Seema Seetharam, Amanda Thorne, Peter Donnelly

ABSTRACT

Pre-surgical studies allow study of the relationship between mutations and response of oestrogen receptor-positive (ER+) breast cancer to aromatase inhibitors (AIs) but have been limited to small biopsies. Here in phase I of this study, we perform exome sequencing on baseline, surgical core-cuts and blood from 60 patients (40 AI treated, 20 controls). In poor responders (based on Ki67 change), we find significantly more somatic mutations than good responders. Subclones exclusive to baseline or surgical cores occur in ∼30% of tumours. In phase II, we combine targeted sequencing on another 28 treated patients with phase I. We find six genes frequently mutated: PIK3CA, TP53, CDH1, MLL3, ABCA13 and FLG with 71% concordance between paired cores. TP53 mutations are associated with poor response. We conclude that multiple biopsies are essential for confident mutational profiling of ER+ breast cancer and TP53 mutations are associated with resistance to oestrogen deprivation therapy. More... »

PAGES

13294

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms13294

DOI

http://dx.doi.org/10.1038/ncomms13294

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1040945504

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27827358


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