EGAS00001000155-sc-20111102 - samples
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PROVIDER: EGAD00001000050 | EGA |
REPOSITORIES: EGA
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Project description:We here describe the first successful construction of a targeted tandem duplication of a large chromosomal segment in Aspergillus oryzae. The targeted tandem chromosomal duplication was achieved by using strains that had 5’ΔpyrG upstream of the region targeted for tandem chromosomal duplication and 3’ΔpyrG downstream of the target region. Consequently, strains bearing a 210-kb targeted tandem chromosomal duplication near the centromeric region of chromosome 8 and strains bearing a targeted tandem chromosomal duplication of a 700-kb region of chromosome 2 were successfully constructed. The strains bearing the tandem chromosomal duplication were efficiently obtained from the regenerated protoplast of the parental strains. However, the generation of the chromosomal duplication did not depend on the introduction of double-stranded breaks (DSBs) by I-SceI. The chromosomal duplications of these strains were stably maintained after five generations of culture under non-selective conditions. The strains bearing the tandem chromosomal duplication in the 700-kb region of chromosome 2 showed highly increased protease activity in solid-state culture, indicating that the duplication of large chromosomal segments could be a useful new breeding technology and gene analysis method.
2014-06-30 | GSE57246 | GEO
Project description:We here describe the first successful construction of a targeted tandem duplication of a large chromosomal segment in Aspergillus oryzae. The targeted tandem chromosomal duplication was achieved by using strains that had 5M-bM-^@M-^YM-NM-^TpyrG upstream of the region targeted for tandem chromosomal duplication and 3M-bM-^@M-^YM-NM-^TpyrG downstream of the target region. Consequently, strains bearing a 210-kb targeted tandem chromosomal duplication near the centromeric region of chromosome 8 and strains bearing a targeted tandem chromosomal duplication of a 700-kb region of chromosome 2 were successfully constructed. The strains bearing the tandem chromosomal duplication were efficiently obtained from the regenerated protoplast of the parental strains. However, the generation of the chromosomal duplication did not depend on the introduction of double-stranded breaks (DSBs) by I-SceI. The chromosomal duplications of these strains were stably maintained after five generations of culture under non-selective conditions. The strains bearing the tandem chromosomal duplication in the 700-kb region of chromosome 2 showed highly increased protease activity in solid-state culture, indicating that the duplication of large chromosomal segments could be a useful new breeding technology and gene analysis method. A. oryzae strain bearing a 210-kb targeted tandem chromosomal duplication, A. oryzae strain bearing a 700-kb targeted tandem chromosomal duplication, and A. oryzae RIB40 (wild type strain), were cultivated in Polypeptone-dextrin medium. After 3 days cultivation, genomic DNAs from the samples were extracted, and array CGH analysis was carried out to confirm the chromosomal duplications in the strains.
2014-06-30 | E-GEOD-57246 | biostudies-arrayexpress
Project description:Small ~10 kb microhomology-mediated tandem duplications (“Group 1 TDs”) are abundant in BRCA1-linked but not BRCA2-linked breast cancer genomes. Here, we define the mechanism underlying this rearrangement signature. We show that BRCA1, but not BRCA2, suppresses TDs at a Tus/Ter site-specific chromosomal replication fork barrier in primary mammalian cells. BRCA1 has no equivalent role at chromosomal double strand breaks, indicating specificity for the stalled fork response. Two motor proteins—FANCM and the Bloom’s syndrome helicase—suppress Tus/Ter-induced TDs in BRCA1 mutants, revealing the existence of a multi-gene TD suppressor network. TDs arise by a “replication restart-bypass” mechanism terminated by end joining or microhomology-mediated template switching, the latter forming complex TD breakpoints. We show that solitary DNA ends form directly at Tus/Ter, implicating misrepair of these lesions in TD formation. We find that BRCA1 inactivation is strongly associated with Group 1 TDs in ovarian cancer. The Group 1 TD phenotype may be a general signature of BRCA1-deficient cancer
2017-11-23 | GSE103624 | GEO
Project description:Chromosomal structural mutations play an important role in determining the transcriptional landscape of human breast cancers. To assess the nature of these structural mutations, we analyzed a representative sampling of the major types of breast tumor samples for detailed structural mutations using paired-end tag sequencing of long-insert genomic DNA (DNA-PET) with matched transcriptome ascertainment by RNA-seq. Compared with other structural mutations, tandem duplications are enriched around partners of fusion transcripts and demarcate regions of high gene expression. Moreover tandem duplications appear to be early events in tumor evolution by facilitating subsequent downstream amplification and deletion of important adjacent cancer associated genes. In a detailed reconstruction of events in chr17, we found large unpaired-inversions connect a duplicated ERBB2 with neighboring 17q21.3 amplicons while simultaneously deleting the intervening BRCA1 tumor suppressor locus. Using siRNAs in breast cancer cell lines, we showed that the 17q21.3 amplicon harbored a significant number of weak oncogenes that appeared consistently co-amplified in primary tumors. Down-regulation of BRCA1 expression augmented the cell proliferation in human normal mammary epithelial cells. Finally, using in silico approaches, we determined that genes whose expression in breast tumors are associated with either poor or good clinical prognosis appear clustered together in segments of frequent amplification or deletion, suggesting that structural abnormalities induce the loss or gain of blocks of adjacent genes with oncogenic or growth suppressor function. These analyses suggest that structural mutations efficiently orchestrate the gain and loss of cancer gene cassettes that engage many oncogenic pathways simultaneously. RNA sequencing of four primary breast cancer RNA samples (SOLiD, Applied Biosystems).
2014-07-01 | E-GEOD-57914 | biostudies-arrayexpress
Project description:We investigated the CNAs in a four stage tumorigenesis model. This model included copy number analyses in non-transgenic NMRI mice (normal) and in transgenic SVT/t mice: non-malignant hyperplastic mammary glands and breast cancers, as well as breast cancer derived cell lines. We focused our research on copy number analyses to compare the genomic alterations that occur during tumorigenesis. We addressed the question, whether common predisposed chromosomal breakpoints could be seen to promote malignant transformation. We can report a characteristic increase of copy number alterations from normal to tumor stage in our model. Furthermore, we have identified chromosomal segments and found characteristic fragmentations.
2012-09-04 | GSE35873 | GEO
Project description:High-grade serous ovarian carcinoma (HGSOC) is the most genomically complex cancer, characterised by ubiquitous TP53 mutation, profound structural variation and heterogeneity. Multiple mutational processes driving chromosomal instability can be distinguished by specific copy number signatures. To develop clinically relevant models of these mutational processes we derived 15 continuous HGSOC patient-derived organoids (PDOs) and provide detailed transcriptomic and genomic profiles using shallow whole genome sequencing single cell and bulk analysis. We show that PDOs comprise communities of different clonal populations and represent models of CCNE1 amplification, chromothripsis, tandem-duplicator phenotype and whole genome duplication. PDOs can also be used as exploratory tools to study transcriptional effects of copy number alterations as well as compound-sensitivity tests. In summary, HGSOC PDO cultures provide a genomic tool for studies of specific mutational processes and precision therapeutics.
2022-07-17 | GSE208216 | GEO
Project description:Intra-individual tumoral heterogeneity (ITH) is a hallmark of solid tumors and impedes accurate genomic diagnosis and selection of proper therapy. The purpose of this study was to identify ITH of ovarian serous adenocarcinomas (OSAs) and to determine the utility of ascitic cancer cells as a resource for mutation profiling in spite of ITH. We performed whole-exome sequencing, copy number profiling, and DNA methylation profiling of four OSA genomes using multiregional biopsies from 13 intraovarian lesions, 12 extraovarian tumor lesions (omentum/peritoneum), and ascitic cells. We observed substantial levels of heterogeneity in mutations and copy number alterations (CNAs) of the OSAs. We categorized the mutations into 'common', 'shared' and 'private' according to the regional distribution. Six common, 8 shared, and 24 private mutations were observed in known cancer-related genes,. but common mutations had a higher mutant allele frequency and included TP53 mutations in all four OSAs. Region-specific chromosomal amplifications and deletions involving BRCA1, PIK3CA, and RB1 were also identified. Of note, the mutations detected in ascitic cancer cells represented 92.3-100% of overall somatic mutations in the given case. Phylogenetic analyses of ascitic genomes predicted a polyseeding origin of somatic mutations in ascitic cells. Our results demonstrate that despite ITH, somatic mutations, CNAs, and DNA methylations in both âcommonâ category and cancer-related genes were highly conserved in ascitic cells of OSAs, highlighting the clinical relevance of genome analysis of ascitic cells. Ascitic tumor cells may serve as a potential resource to discover somatic mutations of primary OSA with diagnostic and therapeutic relevance. The purpose of this study was to identify intra-individual tumor heterogenety of ovarian serous adenocarcinomas Four to nine different ovarian cancer areas from intraovarian and extra-ovarian lesions that were at least 1cm apart as well as 50 ml ascites were collected from the four OSA patients. Genomic DNA from tumor and matched normal samples were simultaneously hybridized onto the array. Total 29 array experiments were conducted.
2016-08-09 | E-GEOD-85295 | biostudies-arrayexpress
Project description:Breast and ovarian cancers, the most common cancers in women in India. Metastatic organotropism is a non-random, predetermined process which represents a more lethal and advanced form of cancer with increased mortality rate. In an attempt to study organotropism, salivary proteins were analyzed by mass spectrometry indicative of pathophysiology of breast and ovarian cancers compared to healthy and ovarian chemotherapy subjects. Collectively, 646 proteins were identified, of which 409 proteins were confidently identified across all four groups. Network analysis of up-regulated proteins such as coronin-1A, hepatoma derived growth factor, vasodilator-stimulated phosphoprotein (VASP), and cofilin in breast cancer and proteins like coronin-1A, destrin and HSP90α in ovarian cancer were functionally linked and were known to regulate cell proliferation and migration. Additionally, proteins namely VASP, coronin-1A, stathmin and suprabasin were confidently identified in ovarian chemotherapy subjects, possibly in response to combined paclitaxel and carboplatin drug therapy to ovarian cancer. In summary, this proteomic study was performed to identify a pattern of differentially expressed salivary proteins as indicators of metastatic organotropism potential of breast and ovarian cancers, as well as their response to neoadjuvant (paclitaxel and carboplatin) drugs therapy.
2020-05-26 | PXD011541 | Pride
Project description:The identification and characterization of subpopulations of cancer stem cells (CSCs) provide new understandings and possible therapeutic implications in cancer biology. We found the ovarian cancer sphere cells possessed CSCs properties maintained self renewal, drug resistance, and tumorigenesis. Using high-throughput microarray system, we identified common GO terms and pathway signatures significantly enriched in ovarian and breast cancer stem cells. Ovarian and breast cancer cells were cultured in sphere formation conditions, and total RNA from those spheres and conresponding adhered cell was hybridized on Affymetrix microarrays.
2013-11-25 | E-GEOD-43657 | biostudies-arrayexpress
Project description:Duplication of chromosomal arm 20q occurs in prostate, cervical, colon, gastric, bladder, melanoma, pancreas and breast cancer, suggesting that 20q amplification may play a key causal role in tumorigenesis. According to an alternative view, chromosomal instabilities are mainly a common side effect of cancer progression. To test whether a specific genomic aberration might serve as a cancer initiating event, we established an in vitro system that models the evolutionary process of early stages of prostate tumor formation; normal prostate cells were immortalized and cultured for 650 days till several transformation hallmarks were observed. Gene expression patterns were measured and chromosomal aberrations were monitored by spectral karyotype analysis at different times. Several chromosomal aberrations, in particular duplication of chromosomal arm 20q, occurred early in the process and were fixed in the cell populations, while other aberrations became extinct shortly after their appearance. A wide range of bioinformatic tools, applied to our data and to data from several cancer databases, revealed that spontaneous 20q amplification can promote cancer initiation. Our computational model suggests that deregulation of some key pathways, such as MAPK, p53, cell cycle regulation and Polycomb group factors, in addition to activation of several genes like Myc, AML, B-Catenin and the ETS family transcription factors, are key steps in cancer development driven by 20q amplification. Finally we identified 13 cancer initiating genes, located on 20q13, which were significantly overexpressed in many tumors, with expression levels correlated with tumor grade and outcome; these probably play key roles in inducing malignancy via20q amplification. 33 samples were analysised, 12 were in replicate
2010-12-01 | E-GEOD-23038 | biostudies-arrayexpress