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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

Overview of attention for article published in BMC Genomics, July 2017
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Title
Integrative analysis of copy number and gene expression in breast cancer using formalin-fixed paraffin-embedded core biopsy tissue: a feasibility study
Published in
BMC Genomics, July 2017
DOI 10.1186/s12864-017-3867-3
Pubmed ID
Authors

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

Abstract

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 formalin-fixed paraffin-embedded (FFPE) tissue. This study evaluated two platforms available for the analysis of DNA copy number and gene expression using FFPE samples. 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). 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. 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. Trial registration number ISRCTN09184069 and registered retrospectively on 02/06/2010.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 38 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 8 21%
Student > Ph. D. Student 5 13%
Other 4 11%
Professor > Associate Professor 4 11%
Student > Master 3 8%
Other 7 18%
Unknown 7 18%
Readers by discipline Count As %
Medicine and Dentistry 14 37%
Agricultural and Biological Sciences 5 13%
Biochemistry, Genetics and Molecular Biology 3 8%
Pharmacology, Toxicology and Pharmaceutical Science 2 5%
Mathematics 1 3%
Other 1 3%
Unknown 12 32%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 March 2018.
All research outputs
#20,434,884
of 22,988,380 outputs
Outputs from BMC Genomics
#9,318
of 10,690 outputs
Outputs of similar age
#272,460
of 312,560 outputs
Outputs of similar age from BMC Genomics
#197
of 225 outputs
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We're also able to compare this research output to 225 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.