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

• Type of Material: Article
• Authors: Ivanesa Pardo, Indiana University; Heather A. Lillemoe, Indiana University; Rachel J. Blosser, Indiana University; MiRan Choi, Northwestern University; Candice A. M. Sauder, Indiana University; Diane K. Doxey, Indiana University; Theresa Mathieson, Indiana University; Bradley A. Hancock, Indiana University; Dadrie Baptiste, Indiana University; Rutuja Atale, Indiana University; Matthew Hickenbotham, Cofactor Gen LLC; Jin Zhu, Cofactor Gen LLC; Jarret Glasscock, Cofactor Gen LLC; Anna Maria V. Storniolo, Indiana University; Faye Zheng, Purdue University; R.W. Doerge, Purdue University; Yunlong Liu, Indiana University; Sunil Badve, Emory University; Milan Radovich, Indiana University; Susan E. Clare, Northwestern University
• Language: English
• Date: 2014-01-01
• Publisher: BMC
• Publication Version: Final Published Version
• Copyright Statement: © 2014 Pardo et al.; licensee BioMed Central Ltd.
• License: Creative Commons Attribution 2.0 Generic
• Final Published Version (URL): http://dx.doi.org/10.1186/bcr3627
• Title of Journal or Parent Work: BREAST CANCER RESEARCH
• Volume: 16
• Issue: 2
• Start Page: R26
• End Page: R26
• Grant/Funding Information: This work was funded by the Susan G. Komen for the Cure (SEC, AVS, TM), The Breast Cancer Research Foundation (SEC, AVS, MC), the Catherine Peachey Fund (MR, SEC, AVS), the Department of Surgery Indiana University School of Medicine (IP, HAL, RJB, CAMS), and the Department of Medicine, Indiana University School of Medicine (BAH). MR was supported by a predoctoral fellowship from the NIH, NRSA 1 T32 CA 111198 Cancer Biology Training Program. Publication costs were defrayed by donations received at the Solheim Pink Bow Luncheon in Lake Geneva, WI.
• Keywords: BOWEL PROJECT; HOMOLOGOUS RECOMBINATION; Science & Technology; GROWTH-FACTOR FAMILY; Life Sciences & Biomedicine; HUMAN CELL-CYCLE; Oncology; CANCER; FOXM1 EXPRESSION; PROGESTERONE; MAMMARY EPITHELIUM; SURGICAL ADJUVANT BREAST; MENSTRUAL-CYCLE
• Research Categories: Health Sciences, Oncology; Health Sciences, Obstetrics and Gynecology; Biology, Genetics

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.