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Integrative analysis of copy number and gene expression in breast cancer using formalin-fixed paraffin-embedded core biopsy tissue: a feasibility study

Iddawela, Mahesh; Rueda, Oscar; Eremin, Jenny; Eremin, Oleg; Cowley, Jed; Earl, Helena M.; Caldas, Carlos

Authors

Mahesh Iddawela

Oscar Rueda

Jenny Eremin

Oleg Eremin

Jed Cowley

Helena M. Earl

Carlos Caldas



Abstract

Background: An absence of reliable molecular markers has hampered individualised breast cancer treatments, and a major limitation for translational research is the lack of fresh tissue. There are, however, abundant banks of formalinfixed paraffin-embedded (FFPE) tissue. This study evaluated two platforms available for the analysis of DNA copy number and gene expression using FFPE samples.
Methods: The cDNA-mediated annealing, selection, extension, and ligation assay (DASL™) has been developed for gene expression analysis and the Molecular Inversion Probes assay (Oncoscan™), were used for copy number analysis using FFPE tissues. Gene expression and copy number were evaluated in core-biopsy samples from patients with breast cancer undergoing neoadjuvant chemotherapy (NAC).
Results: Forty-three core-biopsies were evaluated and characteristic copy number changes in breast cancers, gains in 1q, 8q, 11q, 17q and 20q and losses in 6q, 8p, 13q and 16q, were confirmed. Regions that frequently exhibited gains in tumours showing a pathological complete response (pCR) to NAC were 1q (55%), 8q (40%) and 17q (40%), whereas 11q11 (37%) gain was the most frequent change in non-pCR tumours. Gains associated with poor survival were 11q13 (62%), 8q24 (54%) and 20q (47%). Gene expression assessed by DASL correlated with immunohistochemistry (IHC) analysis for oestrogen receptor (ER) [area under the curve (AUC) = 0.95], progesterone receptor (PR)(AUC = 0.90) and human epidermal growth factor type-2 receptor (HER-2) (AUC = 0.96). Differential expression analysis between ER+ and ER– cancers identified over-expression of TTF1, LAF-4 and C-MYB (p ≤ 0.05), and between pCR vs non-pCRs, over-expression of CXCL9, AREG, B-MYB and under-expression of ABCG2.
Conclusion: This study was an integrative analysis of copy number and gene expression using FFPE core biopsies and showed that molecular marker data from FFPE tissues were consistent with those in previous studies using fresh-frozen samples. FFPE tissue can provide reliable information and will be a useful tool in molecular marker studies.

Citation

Iddawela, M., Rueda, O., Eremin, J., Eremin, O., Cowley, J., Earl, H. M., & Caldas, C. (in press). Integrative analysis of copy number and gene expression in breast cancer using formalin-fixed paraffin-embedded core biopsy tissue: a feasibility study. BMC Genomics, 18(1), https://doi.org/10.1186/s12864-017-3867-3

Journal Article Type Article
Acceptance Date Jun 16, 2017
Online Publication Date Jul 11, 2017
Deposit Date Apr 24, 2018
Publicly Available Date Apr 24, 2018
Journal BMC Genomics
Electronic ISSN 1471-2164
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 18
Issue 1
DOI https://doi.org/10.1186/s12864-017-3867-3
Keywords Gene Expression, Copy Number, FFPE, Genomics, Breast Cancer, DASL, Molecular Inversion Probes Assay, Oncoscan Array, Molecular Markers
Public URL http://eprints.nottingham.ac.uk/id/eprint/51338
Publisher URL https://doi.org/10.1186/s12864-017-3867-3
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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