The functional consequences of missense variants in disease genes are difficult to predict. We assessed if gene expression profiles could distinguish between BRCA1 or BRCA2 pathogenic truncating and missense mutation carriers and familial breast cancer cases whose disease was not attributable to BRCA1 or BRCA2 mutations (BRCAX cases). 72 cell lines from affected women in high-risk breast-ovarian families were assayed after exposure to ionising irradiation, including 23 BRCA1 carriers, 22 BRCA2 carriers, and 27 BRCAX individuals. A subset of 10 BRCAX individuals carried rare BRCA1/2 sequence variants considered to be of low clinical significance (LCS). BRCA1 and BRCA2 mutation carriers had similar expression profiles, with some subclustering of missense mutation carriers. The majority of BRCAX individuals formed a distinct cluster, but BRCAX individuals with LCS variants had expression profiles similar to BRCA1/2 mutation carriers. Gaussian Process Classifier predicted BRCA1, BRCA2 and BRCAX status with a maximum of 62% accuracy, and prediction accuracy decreased with inclusion of BRCAX samples carrying an LCS variant, and inclusion of pathogenic missense carriers. Similarly, prediction of mutation status with gene lists derived using Support Vector Machines was good for BRCAX samples without an LCS variant (82-94%), poor for BRCAX with an LCS (40-50%), and improved for pathogenic BRCA1/2 mutation carriers when the gene list used for prediction was appropriate to mutation effect being tested (71-100%). This study indicates that mutation effect, and presence of rare variants possibly associated with a low risk of cancer, must be considered in the development of array-based assays of variant pathogenicity.
BRCA1 and BRCA2 missense variants of high and low clinical significance influence lymphoblastoid cell line post-irradiation gene expression.
Sex, Age
View SamplesExpression profile of 30 LMP tumours and 60 Serous tumours were compared to identify the biolgical pathways specific to these groups. Genotyping was done to identify the mutations potentially causing these phenotypes
Mutation of ERBB2 provides a novel alternative mechanism for the ubiquitous activation of RAS-MAPK in ovarian serous low malignant potential tumors.
No sample metadata fields
View SamplesMacrophages in tumor microenvironment have been characterized as M1- and M2-polarized subtypes. This study sought to investigate the effects of different macrophage subtypes on the biological behavior and global gene expression profiles of lung cancer cells. Expression microarray and bioinformatics analyses indicated that the different macrophage subtypes mainly regulated genes involved in cell cycle, cytoskeletal remodeling, coagulation, cell adhesion and apoptosis pathways in A549 cells, a pattern that correlated with the altered behavior of A549 cells observed after coculture with macrophage subtypes.
Opposite Effects of M1 and M2 Macrophage Subtypes on Lung Cancer Progression.
Specimen part, Cell line
View SamplesIn order to identify patterns of gene expression associated with biological effects in THP-1 cells induced by F3, we performed a transcriptomic analysis on the THP-1 control and F3-treated THP-1 cells by oligonucleotide microarray
Ganoderma lucidum polysaccharides in human monocytic leukemia cells: from gene expression to network construction.
Cell line
View SamplesThe CLS1/CAF co-culture maintained the cancer stemness. This cancer stemness was lost when the CAF feeder cells were removed during passaging.
Cancer-associated fibroblasts regulate the plasticity of lung cancer stemness via paracrine signalling.
Cell line
View SamplesThe mammary gland at early stages of pregnancy undergoes fast cell proliferation, yet the mechanism to ensure its genome integrity is largely unknown. Here we show that pregnancy enhances expression of genes involved in numerous pathways, including most genes encoding replisomes. In mouse mammary glands, replisome genes are positively regulated by estrogen/ERa signaling but negatively regulated by BRCA1. Upon DNA damage, BRCA1 deficiency markedly enhances DNA replication initiation. BRCA1 deficiency also preferably impairs DNA replication checkpoints mediated by ATR and CHK1 but not by WEE1, which inhibits DNA replication initiation through CDC7-MCM2 pathway and enables BRCA1-deficient cells to avoid further genomic instability. Thus, BRCA1 and WEE1 inhibit DNA replication initiation in a parallel manner to ensure genome stability for mammary gland development during pregnancy.
BRCA1 represses DNA replication initiation through antagonizing estrogen signaling and maintains genome stability in parallel with WEE1-MCM2 signaling during pregnancy.
No sample metadata fields
View SamplesWe report the high-throughput profiling of brain RNA from three Drosophila stains: dBRWD3PX2/+, dBRWD3PX2/PX2 and dBRWD3PX2/PX2, yemGS21861/GS21861. By obtaining over 50 million reads of sequence, WE compared the transcriptomic differences among the brains from these three stains. We found that the expression of 871 genes was significantly different between heterozygous control and homozygous dBRWD3 mutant brains (484 upregulated genes, 387 downregulated genes, p<0.05). Gene ontology (GO) analysis of the 871 genes revealed a broad spectrum of biological processes, ranging from synaptic activity to housekeeping metabolism subjective to dBRWD3 regulation. Among the 387 downregulated genes, the expression of 360 genes (92.8%) was increased in the dBRWD3, yem double mutant brains compared with dBRWD3 mutant. Among the 484 upregulated genes, the expression of 412 genes (85.1%) was decreased in the double mutant brains. These differential genes were evenly distributed on X chromosome and autosomes (149 on X, 178 on 2L, 154 on 2R, 166 on 3L, and 207 on 3R). These analyses indicate that dBRWD3 regulates gene expression in the brain mainly through the HIRA/YEM complex. Overall design: Examination of brain transcriptome in 3 Drosophila strains.
Intellectual disability-associated dBRWD3 regulates gene expression through inhibition of HIRA/YEM-mediated chromatin deposition of histone H3.3.
Specimen part, Cell line, Subject
View SamplesEpstein-Barr virus (EBV) Rta is a latent-lytic molecular switch evolutionarily conserved in all gamma-herpesviruses. In previous studies, doxycycline-inducible Rta was shown to potently produce an irreversible G1 arrest followed by cellular senescence in 293 cells. Here, we demonstrate that in this system the inducible Rta not only reactivates resident genome of EBV but also that of Kaposis sarcoma-associated herpesvirus (KSHV), to similar efficiency. However, Rta-induced senescence program was terminated by the robust viral lytic cycle replication that eventually caused cell death. Furthermore, prior to the abrupt expression of immediate-early protein (EBV BZLF1 or KSHV RTA), Rta simultaneously down-regulates cell cycle activators (c-Myc, CDK6, CCND2) and up-regulates senescence-related genes (p21, 14-3-3s). Since Rta is a viral immediate-early transcriptional activator, it is envisioned that during the initial stage of viral reactivation, Rta may engage to modulate the host transcriptome, to halt cell cycle progression, and to maintain an ideal environment for manufacturing infectious virions.
Epstein-Barr virus (EBV) Rta-mediated EBV and Kaposi's sarcoma-associated herpesvirus lytic reactivations in 293 cells.
Specimen part, Cell line
View SamplesEBV Rta is a transcriptional activator that functions to disrupt EBV latency in cells of epithelial origin. This series of experiment is to identify host genes that are moduated by the expression of doxycycline-inducible EBV Rta in HEK293 cells. Designations for the pooled EBV Rta inducible cell lines is 293TetER; pooled luciferase inducible lines is 293TetLuc (control).
Epstein-Barr virus (EBV) Rta-mediated EBV and Kaposi's sarcoma-associated herpesvirus lytic reactivations in 293 cells.
Specimen part, Cell line
View SamplesEBV Rta is a transcriptional activator that functions to disrupt EBV latency in cells of epithelial origin. This series of experiment is to identify host genes that are moduated by the expression of doxycycline-inducible EBV Rta in nasopharyngeal carcinoma cells. Designations for the two EBV Rta inducible cell lines are TW01TetER_cl7 (lower expression level) and TW01TetER_cl19 (higher expression level); for the control line is TW01Tet.
Epstein-Barr virus (EBV) Rta-mediated EBV and Kaposi's sarcoma-associated herpesvirus lytic reactivations in 293 cells.
Specimen part, Cell line
View Samples