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Series GSE28514 Query DataSets for GSE28514
Status Public on Apr 11, 2011
Title microRNA expression profiling of lobular neoplasia
Organism Homo sapiens
Experiment type Non-coding RNA profiling by array
Summary Invasive lobular carcinoma (ILC) of the breast accounts for 5-15% of breast cancers and is characterized by loss of E-cadherin and believed to arise via a linear histological progression. Genomic studies have identified a clonal relationship between ILC and concurrent lobular carcinoma in situ (LCIS) lesions, suggesting that LCIS may be a precursor lesion. It has been shown that an LCIS diagnosis confers a 15-20% risk of progression to ILC, over a lifetime. Currently no molecular test or markers can identify LCIS lesions likely to progress to ILC. Since microRNA (miRNA) expression changes have been detected in a number of other cancer types, we explored whether their dysregulation might be detected during progression from LCIS to ILC. Using the Illumina miRNA profiling platform, designed for simultaneous analysis of 470 mature miRNAs, we analyzed the profiles of archived normal breast epithelium, LCIS lesions found alone, LCIS lesions concurrent with ILC, and the concurrent ILCs, as a model of linear histological progression toward ILC. We identified two sets of differentially expressed miRNAs, the first set highly expressed in normal epithelium, including hsa-miR-224, -139, -10b, -450, 140 and -365 and the second set upregulated during lobular neoplasia, including hsa-miR-375, -203, -425-5p, -183, -565 and -182. Using quantitative RT-PCR, we validated a trend of increased expression for hsa-mir-375, hsa-mir-182, and hsa-mir-183 correlating with ILC progression. As we detected increased expression of hsa-miR-375 in LCIS lesions synchronous with ILC, we sought to determine whether hsa-mir-375 might induce phenotypes reminiscent of lobular neoplasia by expressing it in the MCF10A 3D culture model of mammary acinar morphogenesis. Increased expression of hsa-miR-375 resulted in loss of cellular organization and acquisition of a hyperplastic phenotype. These data suggest that dysregulated miRNA expression contributes to lobular neoplastic progression.
Overall design 6 specimens were analyzed in duplicate. One frozen normal lobular epithelium and the matched FFPE (1 month old) normal lobular epithelium. One lobular carcinoma in situ (LCIS) found alone, one LCIS synchronous with an invasive lobular carcinoma (ILC), the synchronous ILC (from a different archived block), and one ILC found alone without presence of any other breast cancer.
Contributor(s) Fineberg S, Shapiro N, Loudig O, Liu C
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Submission date Apr 11, 2011
Last update date Mar 23, 2012
Contact name olivier D Loudig
Phone 718-430-3430
Fax 718-4308780
Organization name Albert Einstein College of Medicine
Department Epidemiolkogy and Population Health
Street address 1300 Morris Park Avenue
City Bronx
State/province New York
ZIP/Postal code 10461
Country USA
Platforms (1)
GPL8178 Illumina Human v1 MicroRNA expression beadchip
Samples (12)
GSM706270 normal_Frozen_breast epithelium_rep1
GSM706271 normal_Frozen_breast epithelium_rep2
GSM706272 normal_FFPE_breast epithelium_rep1
BioProject PRJNA138975

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE28514_RAW.tar 50.0 Kb (http)(custom) TAR
GSE28514_non-normalized_data.txt.gz 169.0 Kb (ftp)(http) TXT
Processed data included within Sample table

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