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Open Access Highly Accessed Research article

Next-generation transcriptome sequencing of the premenopausal breast epithelium using specimens from a normal human breast tissue bank

Ivanesa Pardo2, Heather A Lillemoe2, Rachel J Blosser2, MiRan Choi1, Candice A M Sauder2, Diane K Doxey2, Theresa Mathieson3, Bradley A Hancock4, Dadrie Baptiste2, Rutuja Atale2, Matthew Hickenbotham5, Jin Zhu5, Jarret Glasscock5, Anna Maria V Storniolo34, Faye Zheng6, RW Doerge6, Yunlong Liu7, Sunil Badve8, Milan Radovich2, Susan E Clare1* and On behalf of the Susan G. Komen for the Cure Tissue Bank at the IU Simon Cancer Center

Author Affiliations

1 Department of Surgery, Feinberg School of Medicine, Northwestern University, 303 East Superior Street, Chicago, IL 60611, USA

2 Department of Surgery, Indiana University School of Medicine, 980 West Walnut Street, Indianapolis, IN 46202, USA

3 Susan G. Komen for the Cure Tissue Bank at the IU Simon Cancer Center, 550 University Boulevard, Indianapolis, IN 46202, USA

4 Department of Medicine, Indiana University School of Medicine, 535 Barnhill Drive, Indianapolis, IN 46202, USA

5 Cofactor Genomics, LLC, 3139 Olive Street, St. Louis, MO 631036, USA

6 Department of Statistics, Purdue University, 150 North University Street, West Lafayette, IN 47907, USA

7 Department of Medical and Molecular Genetics, Indiana University School of Medicine, 410 West 10th Street, Indianapolis, IN 46202-5122, USA

8 Department of Pathology, Indiana University School of Medicine, 350 West 11th Street, Indianapolis, IN 46202-4108, USA

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Breast Cancer Research 2014, 16:R26  doi:10.1186/bcr3627

Published: 17 March 2014

Abstract

Introduction

Our efforts to prevent and treat breast cancer are significantly impeded by a lack of knowledge of the biology and developmental genetics of the normal mammary gland. In order to provide the specimens that will facilitate such an understanding, The Susan G. Komen for the Cure Tissue Bank at the IU Simon Cancer Center (KTB) was established. The KTB is, to our knowledge, the only biorepository in the world prospectively established to collect normal, healthy breast tissue from volunteer donors. As a first initiative toward a molecular understanding of the biology and developmental genetics of the normal mammary gland, the effect of the menstrual cycle and hormonal contraceptives on DNA expression in the normal breast epithelium was examined.

Methods

Using normal breast tissue from 20 premenopausal donors to KTB, the changes in the mRNA of the normal breast epithelium as a function of phase of the menstrual cycle and hormonal contraception were assayed using next-generation whole transcriptome sequencing (RNA-Seq).

Results

In total, 255 genes representing 1.4% of all genes were deemed to have statistically significant differential expression between the two phases of the menstrual cycle. The overwhelming majority (221; 87%) of the genes have higher expression during the luteal phase. These data provide important insights into the processes occurring during each phase of the menstrual cycle. There was only a single gene significantly differentially expressed when comparing the epithelium of women using hormonal contraception to those in the luteal phase.

Conclusions

We have taken advantage of a unique research resource, the KTB, to complete the first-ever next-generation transcriptome sequencing of the epithelial compartment of 20 normal human breast specimens. This work has produced a comprehensive catalog of the differences in the expression of protein-coding genes as a function of the phase of the menstrual cycle. These data constitute the beginning of a reference data set of the normal mammary gland, which can be consulted for comparison with data developed from malignant specimens, or to mine the effects of the hormonal flux that occurs during the menstrual cycle.