title: Next-generation transcriptome sequencing of the premenopausal breast epithelium using specimens from a normal human breast tissue bank.
abstract: BACKGROUND
  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.
authors.forename: Ivanesa
authors.initials: I
authors.lastname: Pardo
authors.forename: Heather A
authors.initials: HA
authors.lastname: Lillemoe
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Blosser
authors.forename: MiRan
authors.initials: M
authors.lastname: Choi
authors.forename: Candice A M
authors.initials: CA
authors.lastname: Sauder
authors.forename: Diane K
authors.initials: DK
authors.lastname: Doxey
authors.forename: Theresa
authors.initials: T
authors.lastname: Mathieson
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Hancock
authors.forename: Dadrie
authors.initials: D
authors.lastname: Baptiste
authors.forename: Rutuja
authors.initials: R
authors.lastname: Atale
authors.forename: Matthew
authors.initials: M
authors.lastname: Hickenbotham
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
authors.forename: Jarret
authors.initials: J
authors.lastname: Glasscock
authors.forename: Anna Maria V
authors.initials: AM
authors.lastname: Storniolo
authors.forename: Faye
authors.initials: F
authors.lastname: Zheng
authors.forename: R W
authors.initials: RW
authors.lastname: Doerge
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Liu
authors.forename: Sunil
authors.initials: S
authors.lastname: Badve
authors.forename: Milan
authors.initials: M
authors.lastname: Radovich
authors.forename: Susan E
authors.initials: SE
authors.lastname: Clare
mesh_terms: D000328:Adult; D000465:Algorithms; D001940:Breast / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism*; D005260:Female; D005498:Follicular Phase / Q000235:genetics; D053263:Gene Regulatory Networks; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D016014:Linear Models; D008183:Luteal Phase / Q000235:genetics; D008875:Middle Aged; D017697:Premenopause / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014015:Tissue Banks; D059467:Transcriptome / Q000235:genetics*