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| Status |
Public on Apr 11, 2011 |
| Title |
microRNA expression profiling of lobular neoplasia |
| Organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
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| 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.
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| 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.
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| Contributor(s) |
Fineberg S, Shapiro N, Loudig O, Liu C |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Apr 11, 2011 |
| Last update date |
Mar 23, 2012 |
| Contact name |
olivier D Loudig |
| E-mail(s) |
olivier.loudig@einstein.yu.edu
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| Phone |
718-430-3430
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| Fax |
718-4308780
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| Organization name |
Albert Einstein College of Medicine
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| Department |
Epidemiolkogy and Population Health
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| Street address |
1300 Morris Park Avenue
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| City |
Bronx |
| State/province |
New York |
| ZIP/Postal code |
10461 |
| Country |
USA |
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| Platforms (1) |
| GPL8178 |
Illumina Human v1 MicroRNA expression beadchip |
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| Samples (12)
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| GSM706270 |
normal_Frozen_breast epithelium_rep1 |
| GSM706271 |
normal_Frozen_breast epithelium_rep2 |
| GSM706272 |
normal_FFPE_breast epithelium_rep1 |
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| Relations |
| BioProject |
PRJNA138975 |
| 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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