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




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Breast Cancer Research

, 16:R26

First Online: 17 March 2014Received: 23 April 2013Accepted: 10 March 2014DOI: 10.1186-bcr3627

Cite this article as: Pardo, I., Lillemoe, H.A., Blosser, R.J. et al. Breast Cancer Res 2014 16: R26. doi:10.1186-bcr3627

Abstract

IntroductionOur 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.

MethodsUsing 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.

ResultsIn 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.

ConclusionsWe 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.

AbbreviationsBERbase excision repair

bpbase pair

CCANconstitutive centromere-associated network

COREContinuing Outcomes Relevant to Evista

CPCchromosome passenger complex

DAB3,3′-diaminobenzidine

DAVIDdatabase for annotation, visualization and integrated discovery

DEdifferential expression

DNAdeoxyribonucleic acid

Ffollicular

ERestrogen receptor

FDRfalse discovery rate

FFPEformalin-fixed, paraffin-embedded

GOGene Ontology

GEFguanine-nucleotide exchange factor

HChormonal contraception

IBIS-1International Breast Cancer Intervention Study-1

IPAIngenuity Pathway Analysis

IUIndiana University

kMTkinetochore-microtubules

KTBThe Susan G. Komen for the Cure Tissue Bank at the IU Simon Cancer Center

Lluteal

LCMlaser capture microdissection

LHluteinizing hormone

MCMminichromosome maintenance

MOREMultiple Outcomes of Raloxifene Evaluation

mRNAmessenger RNA

MTmicrotubule

NBnegative binomial

NCINational Cancer Institute

NSABP-P1The National Surgical Adjuvant Breast and Bowel Project, Breast Cancer Prevention Trial 1

ORCorigin recognition complex

pre-RCpre-replicative complexes

PRprogesterone receptor

RNAribonucleic acid

RNA-Seqwhole transcriptome sequencing

SACspindle assembly checkpoint

siRNAsmall interfering RNA

STARStudy of Tamoxifen and Raloxifene STAR Clinical Trial

TFtranscription factor.

Electronic supplementary materialThe online version of this article doi:10.1186-bcr3627 contains supplementary material, which is available to authorized users.

Ivanesa Pardo, Heather A Lillemoe contributed equally to this work.

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Autor: Ivanesa Pardo - Heather A Lillemoe - Rachel J Blosser - MiRan Choi - Candice A M Sauder - Diane K Doxey - Theresa Math

Fuente: https://link.springer.com/







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