Head and neck cancer is a hetergeneous disease. Based on previoulsy defined molecular subtypes we associated gene expression with response to different compounds. We used microarry gene expression for molecular subtyping
Basal subtype is predictive for response to cetuximab treatment in patient-derived xenografts of squamous cell head and neck cancer.
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Brain transcriptional and epigenetic associations with autism.
Age, Specimen part, Disease, Disease stage, Subject
View SamplesThe LEF/TCF family of transcription factors are downstream effectors of the WNT signaling pathway, which drives colon tumorigenesis. LEF/TCFs have a DNA sequence-specific HMG box that binds Wnt Response Elements (WREs). The E tail isoforms of TCFs are alternatively spliced to include a second DNA binding domain called the C-clamp. We show that induction of a dominant negative C-clamp version of TCF1 (dnTCF1E) induces a p21-dependent stall in the growth of DLD1 colon cancer cells. Induction of a C-clamp mutant did not induce p21 or stall cell growth. Microarray analysis revealed that induction of p21 by dnTCF1EWT correlated with a decrease in expression of p21 suppressors that act at multiple levels from transcription (SP5, YAP1, RUNX1), to RNA stability (MSI2), and protein stability (CUL4A). We show that the C-clamp is a sequence specific DNA binding domain that can make contacts with 5-RCCG-3 elements upstream or downstream of WREs. The C-clamp-RCCG interaction was critical for TCF1E mediated transcriptional control of p21-connected target gene promoters. Our results indicate that a WNT/p21 circuit is driven by C-clamp target gene selection.
A WNT/p21 circuit directed by the C-clamp, a sequence-specific DNA binding domain in TCFs.
Specimen part
View SamplesAutism is a common neurodevelopmental syndrome. Numerous rare genetic etiologies are reported; most cases are idiopathic. To uncover important gene dysregulation in autism we analyzed carefully selected idiopathic autistic and control cerebellar and BA19 (occipital) brain tissues using high resolution whole genome gene expression and DNA methylation microarrays. No changes in DNA methylation were identified in autistic brain but gene expression abnormalities in two areas of metabolism were apparent: down-regulation of genes of mitochondrial oxidative phosphorylation and of protein translation. We also found associations between specific behavioral domains of autism and specific brain gene expression modules related to myelin/myelination, inflammation/immune response and purinergic signaling. This work highlights two largely unrecognized molecular pathophysiological themes in autism and suggests differing molecular bases for autism behavioral endophenotypes.
Brain transcriptional and epigenetic associations with autism.
Age
View SamplesExposure to ultraviolet (UV) irradiation is the major cause of nonmelanoma skin cancer, the most common form of cancer in the United States. UV irradiation has a variety of effects on the skin associated with carcinogenesis, including DNA damage and effects on signal transduction. The alterations in signaling caused by UV regulate inflammation, cell proliferation, and apoptosis. UV also activates the orphan receptor tyrosine kinase and proto-oncogene Erbb2 (HER2/neu). In this study, we demonstrate that the UV-induced activation of Erbb2 regulates the response of the skin to UV. Inhibition or knockdown of Erbb2 before UV irradiation suppressed cell proliferation, cell survival, and inflammation after UV. In addition, Erbb2 was necessary for the UV-induced expression of numerous proinflammatory genes that are regulated by the transcription factors nuclear factor-kappaB and Comp1, including interleukin-1beta, prostaglandin-endoperoxidase synthase 2 (Cyclooxygenase-2), and multiple chemokines. These results reveal the influence of Erbb2 on the UV response and suggest a role for Erbb2 in UV-induced pathologies such as skin cancer.
Erbb2 regulates inflammation and proliferation in the skin after ultraviolet irradiation.
No sample metadata fields
View SamplesExpression data from antigen-experienced Nfat1+/+ and Nfat1-/- CD4+ T cells following 21 days of Plasmodium yoelii 17XNL infection.
The Transcription Factor NFAT1 Participates in the Induction of CD4<sup>+</sup> T Cell Functional Exhaustion during Plasmodium yoelii Infection.
Sex, Specimen part
View SamplesA prevalent hypothesis for the cell-to-cell coordination of the phenomena of early development is that a defined mixture of different mRNA species at specific abundances in each cell determines fate and behavior. With this dataset we explore this hypothesis by quantifying the abundance of every mRNA species in every individual cell of the early C. elegans embryo, for which the exact life history and fate is precisely documented. Overall design: Embryos of the 1-, 2-, 4-, 8- and 16-cell stage were dissected into complete sets of single cells, and each cell from each set was sequenced individually using SMARTer technology. 5-9 replicates were generated for each stage. Most cell identities were unknown upon sequencing, but were deduced from by their transcriptomes post hoc.
A Transcriptional Lineage of the Early C. elegans Embryo.
Specimen part, Subject
View SamplesWe hypothesized that preterm spontaneous labor involves aberrant changes in mRNA expression in the placenta. To test this hypothesis, we interrogated the mRNA levels of >50,000 genes and transcript variants using gene expression microarray (Human Genome U133 Plus 2.0 Array, Affymetrix) on 5 placentas collected from preterm spontaneous delivery (<34 weeks of gestation) and another 5 placentas collected from term spontaneous delivery (38-39 weeks).
Systematic identification of spontaneous preterm birth-associated RNA transcripts in maternal plasma.
Specimen part
View SamplesDifferentially expressed mRNA transcripts in the placenta delivered by term spontaneous labour compared to those delivered by elective term cesarean section.
Systematic identification of spontaneous preterm birth-associated RNA transcripts in maternal plasma.
Specimen part
View SamplesThis study examined the small antral follicles (SAFs) in ovaries of young adult rhesus monkeys following consumption of a western-style diet (WSD), with or without chronically elevated androgen levels since before puberty. Cholesterol or testosterone (T; n=6/group) implants were placed subcutaneously beginning at 1 yr of age, with addition of a WSD (high fat/fructose) at 5.5 yrs. Ovaries from treated females and age-matched controls were collected at 7 yrs of age. Compared to controls, consumption of a WSD, with and without T treatment, increased the numbers of SAFs per ovary (P<0.001), due to the presence of more atretic follicles (P<0.01). Immunostaining for the cellular proliferation markers (pRb and pH3) was greater in granulosa cells of healthy SAFs (P<0.01), while staining for the cell cycle inhibitor (p21) was higher in atretic SAFs (P<0.01). Intense CYP17A1 staining was observed on the theca of SAFs from WSD+/- T groups, compared to controls. Microarray analyses of the transcriptome in SAFs isolated from a subgroup (n=3/grp) of WSD and WSD+T treated females and controls consuming a standard diet, identified mRNA levels for 1944 genes changed >2-fold (p<0.05) among the three groups. Pathway analyses identified several gene pathways altered by WSD and/or WSD+T associated with lipid, carbohydrate and lipid metabolism, plus ovarian processes. Alterations of several SAF mRNAs are similar to those observed in follicular cells from women with PCOS. These data indicate chronic exposure to a WSD in the presence and absence of chronically elevated T alters structure and function of SAFs within primate ovaries.
Western-style diet, with and without chronic androgen treatment, alters the number, structure, and function of small antral follicles in ovaries of young adult monkeys.
Sex, Specimen part
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