Genomic approaches have predicted hundreds of thousands of tissue specific cis-regulatory sequences, but the determinants critical to their function and evolutionary history are mostly unknown1-4. Here, we systematically decode a set of brain enhancers active in the zona limitans intrathalamica (zli), a signaling center essential for vertebrate forebrain development via the secreted morphogen, Sonic hedgehog (Shh)5,6. We apply a de novo motif analysis tool to identify six position-independent sequence motifs together with their cognate transcription factors that are essential for zli enhancer activity and Shh expression in the mouse embryo. Using knowledge of this regulatory lexicon, we discover novel Shh zli enhancers in mice, and a functionally equivalent element in hemichordates, indicating an ancient origin of the Shh zli regulatory network that predates the chordate phylum. These findings establish a paradigm for delineating functionally conserved enhancers in the absence of overt sequence homologies, and over extensive evolutionary distances. Overall design: Gene expression profiles from the mouse zona limitans intrathalamica (ZLI) region at E10.5
Cis-regulatory architecture of a brain signaling center predates the origin of chordates.
Specimen part, Cell line, Subject
View SamplesTime series of eleven breast cancer samples subjected to different cold ischemic stress of up to 3 hr post tumor excision.
Effects of tissue handling on RNA integrity and microarray measurements from resected breast cancers.
Subject
View SamplesThe behavior of breast cancers and their response to neoadjuvant systemic therapy depend on their phenotype which is to a large extent determined by gene expression programs within the cancer cell.
Gene expression, molecular class changes, and pathway analysis after neoadjuvant systemic therapy for breast cancer.
Specimen part, Disease, Disease stage, Treatment
View SamplesThe cancer stem cell model maintains that tumors are organized in a hierarchy driven by tumor initiating cells (TICs), and that patient survival inversely correlates with TIC gene expression. Here we generated a prognostic signature for HER2+ breast cancer from TICs purified from MMTV-Her2/Neu mammary tumors. TICs from this model, identified as Lin-:CD24+:JAG1- at a frequency of 2-5% by serial and single cell transplantation assays, showed elevated expression of proliferation genes and low expression of differentiation genes (compared to non-TIC fraction CD24- of the same tumor).
Seventeen-gene signature from enriched Her2/Neu mammary tumor-initiating cells predicts clinical outcome for human HER2+:ERα- breast cancer.
Specimen part
View SamplesTumor samples were obtained from patients with stage II-III breast cancer before starting neoadjuvant chemotherapy with four cycles of 5-fluorouracil/epirubicin/cyclophosphamide (FEC) followed by four cycles of docetaxel/capecitabine (TX) on US Oncology clinical trial 02-103. Most patients with HER-2-positive cancer also received trastuzumab (H).
Cell line derived multi-gene predictor of pathologic response to neoadjuvant chemotherapy in breast cancer: a validation study on US Oncology 02-103 clinical trial.
Age
View SamplesTriple-negative breast cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy generally have worse outcome; however, some patients with residual tumor after neoadjuvant chemotherapy do not relapse. We hypothesize that there are subgroups of chemoresistant TNBC patients with different prognosis. In this study, 25 chemoresistant samples from 47 neoadjuvant chemotherapy-treated TNBC (The Methodist Hospital) are chosen for study
Identification of prognosis-relevant subgroups in patients with chemoresistant triple-negative breast cancer.
Age, Specimen part, Disease, Disease stage
View SamplesThis is a stage-matched case control study. Cases with clinical diagnosis of Inflammatory Breast Cancer (IBC) were selected after reviewing all medical records of the 440 FNA samples. IBC was defined as signs of erythema and edema (peau dorange) involving at least one third of the skin and rapid clinical presentation. Presence of tumor emboli in the dermal lymphatics of the involved skin in the pathology report was not required for inclusion as IBC. Controls were selected to match for T stage, all T4a-c tumors in the data set were included as controls. IBC breast cancer are all T4d breast cancer.
Different gene expressions are associated with the different molecular subtypes of inflammatory breast cancer.
Age, Disease stage
View SamplesThe behavior of breast cancers and their response to different chemotherapy treatments depend on their phenotype which is to a large extent determined by gene expression programs within the cancer cell.
Evaluation of a 30-gene paclitaxel, fluorouracil, doxorubicin, and cyclophosphamide chemotherapy response predictor in a multicenter randomized trial in breast cancer.
Age, Race
View SamplesWe assess if distinct biological processes might be associated with chemotherapy sensitivity in the different clinical subsets of breast cancers.
Gene pathways associated with prognosis and chemotherapy sensitivity in molecular subtypes of breast cancer.
Age, Specimen part
View SamplesComparison of concordance in single and multi-gene genomic indices from data generated by two different laboratories (MD Anderson Cancer Center (MDA) and Jules Bordet Institute (JBI)) and on two different Affymetrix platforms (U113A and U133_Plus2).
Genomic index of sensitivity to endocrine therapy for breast cancer.
Specimen part, Subject
View Samples