The Institute of Cancer Research - Endocrinology Team

Dac ID Contact Person Email Access Information
EGAC00001000532 Judith Bliss Judith [dot] Bliss [at] icr [dot] ac [dot] uk No additional information is available

This DAC controls 1 dataset:

Dataset ID Description Technology Samples
EGAD00001002651 Presurgical studies allow study of the relationship between mutations and response of estrogen 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 approximately 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. Illumina HiSeq 2000;ILLUMINA, Illumina HiSeq 2000; 443