ENAGenomicsMultiomicsTuschl, Lab of RNA Molecular Biology, Rockefeller Universityhttps://www.ebi.ac.uk/ena/browser/view/PRJNA142969Homo sapiensxref:PubMed:21586611MicroRNAs (miRNAs) regulate many genes critical for tumorigenesis. We profiled miRNAs from 11 normal breast tissues, 17 non-invasive, 151 invasive breast carcinomas, and 6 cell lines by in-house-developed barcoded Solexa sequencing. miRNAs were organized in genomic clusters representing promoter-controlled miRNA expression and sequence families representing seed-sequence-dependent miRNA-target regulation. Unsupervised clustering of samples by miRNA sequence families best reflected the clustering based on mRNA expression available for this sample set. Clustering and comparative analysis of miRNA read frequencies showed that normal breast samples were separated from most non-invasive ductal carcinoma in situ and invasive carcinomas by increased miR-21 (the most abundant miRNA in carcinomas) and multiple decreased miRNA families (including mir-98/let-7), with most miRNA changes apparent already in the non-invasive carcinomas. In addition, patients that went on to develop metastasis demonstrated increased expression of mir-423, and triple negative breast carcinomas were most distinct from other tumor subtypes due to up-regulation of the mir-17~92 cluster. However, absolute miRNA levels between normal breast and carcinomas did not reveal any significant differences. We also discovered two polymorphic nucleotide variations among the more abundant miRNAs miR-181a (T19G) and miR-185 (T16G), but we did not identify nucleotide variations expected for classical tumor suppressor function associated with miRNAs. The differentiation of tumor subtypes and prediction of metastasis based on miRNA levels is statistically possible, but is not driven by deregulation of abundant miRNAs, implicating far fewer miRNAs in tumorigenic processes than previously suggested. Overall design: 21 barcoded sequencing runs, including 185 unique samples and 54 samples in replicate (6 in triplicate and the remaining in duplicate). The details of each sample can be found in Supplementary Tables S1 and S2.ENAHuman Mammary Neoplasm, Breast Carcinoma, primary breast cancer, Carcinoma, RNA, malignant tumor of the breast, breast tumour, Breast Carcinomas, "breast neoplasm" EXACT [MTH:120], determination, Breast Neoplasms, stRNA, Neoplasms, Small Temporal RNA, mammary neoplasm, Mammary Cancers, Human Mammary Neoplasms, Primary, Tumor, "breast tumor" EXACT [NCI2004_11_17:C2910], Human, Breast Malignant Neoplasm, Small, Breast Malignant Tumor, Micro RNA, tumor of the breast, "neoplasm of breast (disorder)" EXACT [SNOMEDCT_2005_07_31:126926005], Mammary Carcinomas, Breast Tumor, BREAST NEOPL, chemical analysis, Neoplasm, sequence, Human Mammary Carcinoma, "mammary tumor" EXACT [CSP2005:2016-0671], NOS, breast tumor, Primary., cancer of the breast, pre-miRNA, neoplasm, Malignant Neoplasm of Breast, tumor of breast, pri miRNA, Carcinomas, BC, Mammary Neoplasms, malignant neoplasm of breast, miRNAs, Human Mammary, Breast Neoplasm, Small Temporal, tumour of the breast, Micro, Temporal RNA, NEOPL BREAST, Mammary Neoplasm, Mammary Carcinoma, Human Mammary Carcinomas, Primary MicroRNA, Cancers, breast neoplasm (disease), miRNA, Primary miRNA, "mammary neoplasm" RELATED [], INSDC_feature:ncRNA, pri-miRNA, primary structure of sequence macromolecule, Cancer of the Breast, neoplasm of breast, tumour of breast, neoplasm of the breast, breast neoplasm, breast cancer, cancer of breast, Malignant Tumor of Breast, Mammary, Mammary Cancer, Breast Tumors, Breast Cancer, Breast Malignant Tumors, MicroRNA, Cancer of Breast, assay, Breast, mammary cancer, cancer, mammary tumor, pre miRNA, Breast Malignant Neoplasms, breast, Tumors, CancerHuman, Modern., human being, Man (Taxonomy), Homo sapiens, man, Man, human, Modern ManfalseHomo sapiensMicroRNA sequence and expression analysis in breast tumors by deep sequencing [miRNA sequence data]2025-09-242013-05-31PRJNA142969GSE29173960621586611