ENAGenomicsMultiomicsTuschl, Lab of RNA Molecular Biology, Rockefeller Universityhttps://www.ebi.ac.uk/ena/browser/view/PRJNA142971Homo 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: mRNA profiles for 161 normal breast and invasive breast carcinomas using NKI Operon V3 arrays These samples have matched entries for miRNA profiles also included in this GEO submission.ENAprimary breast cancer, malignant tumor of the breast, determination, Breast Neoplasms, stRNA, Neoplasms, mammary neoplasm, Mammary Cancers, Human Mammary Neoplasms, Tumor, Human, Small, Breast Malignant Tumor, tumor of the breast, "neoplasm of breast (disorder)" EXACT [SNOMEDCT_2005_07_31:126926005], Breast Tumor, Messenger, BREAST NEOPL, "mammary tumor" EXACT [CSP2005:2016-0671], breast tumor, cancer of the breast, neoplasm, Non Polyadenylated, BC, Mammary Neoplasms, malignant neoplasm of breast, Human Mammary, Small Temporal, Mammary Neoplasm, Polyadenylated Messenger, Mammary Carcinoma, Human Mammary Carcinomas, messenger RNA, miRNA, Primary miRNA, INSDC_feature:ncRNA, pri-miRNA, Cancer of the Breast, neoplasm of breast, template RNA, neoplasm of the breast, breast neoplasm, cancer of breast, Malignant Tumor of Breast, data., Mammary, Mammary Cancer, Breast, mammary cancer, mammary tumor, pre miRNA, Breast Malignant Neoplasms, Tumors, Cancer, Human Mammary Neoplasm, Breast Carcinoma, Carcinoma, RNA, breast tumour, Breast Carcinomas, "breast neoplasm" EXACT [MTH:120], Polyadenylated, Small Temporal RNA, Messenger RNA, Primary, "breast tumor" EXACT [NCI2004_11_17:C2910], Breast Malignant Neoplasm, Micro RNA, Mammary Carcinomas, Poly(A)+ mRNA, chemical analysis, Neoplasm, sequence, INSDC_feature:mRNA, Human Mammary Carcinoma, NOS, Polyadenylated RNA, pre-miRNA, Malignant Neoplasm of Breast, tumor of breast, pri miRNA, Carcinomas, Polyadenylated Messenger RNA, miRNAs, Breast Neoplasm, Poly(A)+ RNA, Non Polyadenylated mRNA, tumour of the breast, protein_coding_transcript, Micro, mRNA, Poly(A) Tail, Temporal RNA, NEOPL BREAST, Non-Polyadenylated, Primary MicroRNA, Cancers, breast neoplasm (disease), "mammary neoplasm" RELATED [], primary structure of sequence macromolecule, Non-Polyadenylated mRNA, tumour of breast, breast cancer, Breast Tumors, Breast Cancer, Breast Malignant Tumors, microarray, MicroRNA, Cancer of Breast, assay, Polyadenylated mRNA, cancer, Poly(A) RNA, breastHuman, Modern., human being, Man (Taxonomy), Homo sapiens, man, Man, human, Modern ManfalseHomo sapiensMicroRNA sequence and expression analysis in breast tumors by deep sequencing [mRNA expression array data]2025-09-242014-02-11PRJNA142971GSE29174960621586611