We used two RNA-Seq methods to measure the the global transcription levels in mouse liver cells. The data here provide insight into the pros and cons of whole transcript method and 3' RNA-Seq method. Overall design: KAPA (whole transcript method) and Lexogen (3' RNA-Seq method) were used to compare global expression in 6 mice of two conditions: 1) 3 normal diet mice 2) 3 iron-loaded diet mice.
A comparison between whole transcript and 3' RNA sequencing methods using Kapa and Lexogen library preparation methods.
Sex, Age, Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Phosphorylated and sumoylation-deficient progesterone receptors drive proliferative gene signatures during breast cancer progression.
Specimen part
View SamplesAnlaysis of the differential gene expression between T47D cells expressing wild type (WT) progesterone receptor isoform B (PR) or SUMOylation-deficient PR molecules.
Phosphorylated and sumoylation-deficient progesterone receptors drive proliferative gene signatures during breast cancer progression.
Specimen part
View SamplesGSM48315-GSM48332: Ten cells from C57Bl/6 male mouse bone marrow (SP or CD8 T cells) were sorted into individual wells of 96-well plates. The mRNA of these cells was amplified by the global single cell RT-PCR method and biotinylated targets were generated after optimal digestion with DNAse I.
Evidence for diversity in transcriptional profiles of single hematopoietic stem cells.
No sample metadata fields
View SamplesThe rediscovery of estrogen receptor (ESR1) mutations in metastatic breast cancer is current clinical scenario. We have modeled the three most frequent ESR1 mutations using stable lentiviral vectors in human breast cancer cell lines, and determined that they confer relative resistance to tamoxifen (Tam) in a cell-type specific manner due to distinct epigenetic changes. Resistance was only observed with concomitant engagement and activation of the insulin growth factor signaling pathway (IGF1R). The ESR1 mutants also exhibited enhanced binding with insulin growth factor receptor beta (IGF1R). The selective estrogen degrader, fulvestrant, significantly reduced the anchorage-independent growth of ESR1 mutant-expressing cells, while the combination treatment with the mTOR inhibitor everolimus, restored Tam sensitivity. Since we detected relatively high frequencies of these three mutations in primary breast tumors, our results suggest that clinical targeted sequencing of both primary and metastatic tumors may be justified and comination therapies considered.
ESR1 mutations affect anti-proliferative responses to tamoxifen through enhanced cross-talk with IGF signaling.
Cell line, Treatment
View SamplesEndocrine therapy in patients with breast cancer can be limited by the problem of resistance. Preclinical studies suggest that complete blockade of the estrogen receptor (ER) combined with inhibition of the epidermal growth factor receptor (EGFR) can overcome endocrine resistance. We tested this hypothesis in a phase II neoadjuvant trial of anastrozole and fulvestrant combined with gefitinib in postmenopausal women with newly diagnosed ER-positive breast cancer. After a baseline tumor core biopsy, patients were randomized to receive anastrozole and fulvestrant (AF) or anastrozole, fulvestrant, and gefitinib (AFG) for 3 weeks. After a second biopsy at 3 weeks, all patients received AFG for 4 months and surgery was done if the tumor was operable. The primary endpoint was best clinical response by RECIST criteria and secondary endpoints were toxicity and change in biomarkers. The study closed after 15 patients were enrolled because of slow accrual. Median patient age was 67 years and median clinical tumor size was 7 cm. Four patients had metastatic disease present. Three patients withdrew before response was assessed. In the remaining twelve patients, there were two complete clinical responses (17%), three partial responses (25%), five had stable disease (41%), and two (17%) had progressive disease. Most common adverse events were rash in four patients, diarrhea in four, joint symptoms in three, and abnormal liver function tests in three. There were no grade 4 toxicities and all toxicities were reversible. At 3 weeks, cell proliferation as measured by Ki-67 was significantly reduced in the AFG group (p value= 0.01) with a parallel reduction in the expression of the Cyclin D1 (p value=0.02). RNA microarray data showed a corresponding decrease in the expression of cell cycle genes. These results suggest that AFG was an effective neoadjuvant therapy and consistently reduced proliferation in ER-positive tumors.
A phase II neoadjuvant trial of anastrozole, fulvestrant, and gefitinib in patients with newly diagnosed estrogen receptor positive breast cancer.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer.
Sex, Age, Specimen part, Disease stage, Race
View SamplesRecent meta-analyses suggest triple-negative breast cancer (TNBC) is a heterogenous disease. In this study we sought to define these TNBC subtypes and identify subtype-specific markers and targets.
Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer.
Sex, Age, Specimen part, Disease stage, Race
View SamplesRecent meta-analyses suggest triple-negative breast cancer (TNBC) is a heterogenous disease. In this study we sought to define these TNBC subtypes and identify subtype-specific markers and targets.
Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer.
Sex, Age, Specimen part, Disease stage, Race
View SamplesGoal: To define the digital transcriptome of three breast cancer subtypes (TNBC, Non-TNBC, and HER2-positive) using RNA-sequencing technology. To elucidate differentially expressed known and novel transcripts, alternatively spliced genes and differential isoforms and lastly expressed variants in our dataset. Method: Dr. Suzanne Fuqua (Baylor College of Medicine) provided the human breast cancer tissue RNA samples. All of the human samples were used in accordance with the IRB procedures of Baylor College of Medicine. The breast tumour types, TNBC, Non-TNBC and HER2-positive, were classified on the basis of immunohistochemical and RT-qPCR classification. Results: Comparative transcriptomic analyses elucidated differentially expressed transcripts between the three breast cancer groups, identifying several new modulators of breast cancer. We discovered subtype specific differentially spliced genes and splice isoforms not previously recognized in human transcriptome. Further, we showed that exon skip and intron retention are predominant splice events in breast cancer. In addition, we found that differential expression of primary transcripts and promoter switching are significantly deregulated in breast cancer compared to normal breast. We also report novel expressed variants, allelic prevalence and abundance, and coexpression with other variation, and splicing signatures. Additionally we describe novel SNPs and INDELs in cancer relevant genes with no prior reported association of point mutations with cancer Overall design: mRNA profiles of 17 breast tumor samples of three different subtypes (TNBC, non-TNBC and HER2-positive) and normal human breast organoids (epithelium) samples (NBS) were sequenced using Illumina HiSeq.
Novel insights into breast cancer genetic variance through RNA sequencing.
No sample metadata fields
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