Lopez-Knowles, E., Gao, Q., Cheang, M. C. U., Morden, J., Parker, J., Martin, L. A., Pinhel, I., McNeill, F., Hills, M., Detre, S., Afentakis, M., Zabaglo, L., Dodson, A., Skene, A., Holcombe, C., Robertson, J., Smith, I., Bliss, J. M., Dowsett, M., Trialists, Poetic (2016) Heterogeneity in global gene expression profiles between biopsy specimens taken peri-surgically from primary ER-positive breast carcinomas. BREAST CANCER RESEARCH, 18. ISSN 1465-5411

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Abstract

Background: Gene expression is widely used for the characterisation of breast cancers. Variability due to tissue heterogeneity or measurement error or systematic change due to peri-surgical procedures can affect measurements but is poorly documented. We studied the variability of global gene expression between core-cuts of primary ER+ breast cancers and the impact of delays to tissue stabilisation due to sample X-ray and of diagnostic core cutting. Methods: Twenty-six paired core-cuts were taken immediately after tumour excision and up to 90 minutes delay due to sample X-ray; 57 paired core-cuts were taken at diagnosis and 2 weeks later at surgical excision. Whole genome expression analysis was conducted on extracted RNA. Correlations and differences were assessed between the expression of individual genes, gene sets/signatures and intrinsic subtypes. Results: Twenty-three and 56 sample pairs, respectively, were suitable for analysis. The range of correlations for both sample sets were similar with the majority being >0.97 in both. Correlations between pairs for 18 commonly studied genes were also similar between the studies and mainly with Pearson correlation coefficients >0.6 except for a small number of genes, which had a narrow-dynamic range (e.g. MKI67, SNAI2). There was no systematic difference in intrinsic subtyping between the first and second sample of either set but there was c.15 % discordance between the subtype assignments between the pairs, mainly where the subtyping of individual samples was less certain. Increases in the expression of several stress/early-response genes (e.g. FOS, FOSB, JUN) were found in both studies and confirmed findings in earlier smaller studies. Increased expression of IL6, IGFBP2 and MYC (by 17 %, 14 % and 44 %, respectively) occurred between the samples taken 2 weeks apart and again confirmed findings from an earlier study. Conclusions: There is generally good correlation in gene expression between pairs of core-cuts except where genes have a narrow dynamic range. Similar correlation coefficients to the average gene expression profiles of intrinsic subtype, particularly LumA and LumB, can lead to discordances between assigned subtypes. Substantial changes in expression of early-response genes occur within an hour after surgery and in IL6, IGFB2 and MYC as a result of diagnostic core-cut biopsy.

Item Type:	Article
Authors (ICR Faculty only):	Bliss, Judith and Dowsett, Mitch and Martin, Lesley-Ann and Smith, Ian
All Authors:	Lopez-Knowles, E., Gao, Q., Cheang, M. C. U., Morden, J., Parker, J., Martin, L. A., Pinhel, I., McNeill, F., Hills, M., Detre, S., Afentakis, M., Zabaglo, L., Dodson, A., Skene, A., Holcombe, C., Robertson, J., Smith, I., Bliss, J. M., Dowsett, M., Trialists, Poetic
Additional Information:	ISI Document Delivery No.: DI0LU Times Cited: 0 Cited Reference Count: 14 Lopez-Knowles, Elena Gao, Qiong Cheang, Maggie Chon U. Morden, James Parker, Joel Martin, Lesley-Ann Pinhel, Isabel McNeill, Fiona Hills, Margaret Detre, Simone Afentakis, Maria Zabaglo, Lila Dodson, Andrew Skene, Anthony Holcombe, Chris Robertson, John Smith, Ian Bliss, Judith M. Dowsett, Mitch Mary-Jean Mitchell Green Foundation; Breast Cancer Now Research Centre; National Health Service (NHS); Cancer Research UK This study was funded in part by Mary-Jean Mitchell Green Foundation, Breast Cancer Now Research Centre. We acknowledge National Health Service (NHS) funding to the National Institute for Health Research (NIHR) Biomedical Research Centre at the Royal Marsden Hospital. The POETIC trial (C1491/A8671/CRUK/07/015, C1491/A15955, C406/A8962), from which samples were obtained for this study, was supported by Cancer Research UK as is the Institute of Cancer Research Clinical Trials and Statistics Unit (ICR-CTSU) through its core programme grant. The study sponsors had no involvement in the design of this study, the literature review, data interpretation, writing of the manuscript or the decision to submit it for publication. 0 BIOMED CENTRAL LTD LONDON BREAST CANCER RES
Uncontrolled Keywords:	Breast cancer Gene expression Heterogeneity CANCER-TISSUE THERAPY
Research teams:	Clinical Units > Breast Unit ICR divisions > Clinical Studies > Clinical Trials & Statistics Unit ICR divisions > Breast Cancer Research > Endocrinology ICR divisions > Molecular Pathology > Endocrinology
Depositing User:	Barry Jenkins
Date Deposited:	25 Apr 2016 10:21
Last Modified:	25 Apr 2016 10:35
URI:	http://publications.icr.ac.uk/id/eprint/14982

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