Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA130223 | ENA |
REPOSITORIES: ENA
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Project description:Aneuploidy from chromosomal instability is frequently detected in the vast majority of sporadic colorectal cancer patients and is believed to be an early driving force in disease progression. Despite this observation, the cellular advantages conferred by these cytogenetic alterations are poorly understood. We have isolated and immortalized non-transformed human colonic epithelial cells (HCECs) from non-cancerous biopsy tissue from a previous CRC patient undergoing routine colonoscopy. While these cells maintain a diploid karyotype under 2% serum conditions, we have isolated derivatives in serum-free culture with an extra copy of chromosome 7 (+7), a non-random trisomy detected in over 40% of human colorectal adenomas and carcinomas. We report here that +7 HCECs were not detectable in the initial cell population and appeared from an originally diploid population under serum-free culture conditions. The emergence of +7 cells correlates with a slight growth advantage that may be attributed to aberrant regulation of the epidermal growth factor receptor. We also provide evidence that +7 HCECs have defects in cell migration. A subpopulation with trisomy 20, another non-random chromosomal alteration in CRC, emerged following stable knockdown of TP53 and expression of oncogenic K-RASV12 in +7 HCECs. We describe isogenic HCECs that represent non-random cytogenetic changes occurring in sporadic colorectal cancer progression. These unique cellular reagents may serve as useful in vitro models for studying chromosomal instability-mediated tumorigenesis and the discovery of novel chemopreventive strategies.
2010-09-14 | GSE24092 | GEO
Project description:Heterozygous CHMs have been believed as synonymous with dispermic moles (two sperm origin). The possibility of diploid sperm origin has not been considered. We assessed whether heterozygous CHMs would be of dispermic or diploid sperm origin. In all the cases, centromeric zygosity was random, i.e., mixed status. Theoretically, if the heterozygous CHMs were of diploid sperm origin, the centromeric status will be all homozygous or all heterozygous. Thus, all the analyzed heterozygous CHMs were considered to be of dispermic origin. Three cases showed the trisomy while we did not notice them with STR analysis. Diploid sperm fertilization can be rare during the development of heterozygous androgenetic CHM.
2019-08-31 | GSE117672 | GEO
Project description:Human Neural progenitor cells have been found to have karyotypic abnormalities. In this study we explored the gene changes between hNPCs that are karyotypically normal and hNPCs with a trisomy of chromosome 7. We used Affymetrix GeneChips to study gene expression changes between karyotypically normal hNPCs and trisomy 7 hNPCs. Cells grown in culture for ~20 passages from diploid and + 7 hNPCs were selected for RNA extraction and hybridization on Affymetrix microarrays.
2009-10-01 | E-GEOD-18349 | biostudies-arrayexpress
Project description:Human pluripotent stem cells (hPSCs) tend to acquire genomic aberrations in culture, the most common of which is the trisomy of chromosome 12. Interestingly, trisomy 12 is also prevalent in germ cell tumors (GCTs). Here, we aimed to dissect the cellular and molecular implications of trisomy 12 in hPSCs. A genome-wide gene expression analysis revealed that trisomy 12 profoundly affects the global gene expression profile of hPSCs, inducing a transcriptional program very similar to that of CGTs. Direct comparison of the proliferation, replication, differentiation and apoptosis between diploid and aneuploid hPSCs revealed that trisomy 12 significantly increases the proliferation rate of hPSCs. Increased replication largely accounts for the increased proliferation observed, and may explain the selection advantage that trisomy 12 confers to hPSCs. A comparison of the tumors induced by diploid and aneuploid hPSCs further demonstrated that trisomy 12 increases the tumorigenicity of hPSCs, inducing transcriptionally-distinct teratomas, from which pluripotent cells can be recovered. Lastly, a chemical screen of 89 anticancer drugs against diploid and aneuploid hPSCs discovered that trisomy 12 raises the sensitivity of hPSCs to several replication inhibitors, suggesting that the increased proliferation and tumorigenicity of these aberrant cells also makes them more vulnerable, and might potentially be used for their selective elimination from culture. Together, our findings demonstrate the extensive effect of trisomy 12 on the gene expression signature and on the cellular behavior of hPSCs, and highlight the danger posed by this trisomy for the successful use of hPSCs in basic research and in regenerative medicine.
2014-09-01 | GSE51455 | GEO
Project description:Human pluripotent stem cells (hPSCs) tend to acquire genomic aberrations in culture, the most common of which is the trisomy of chromosome 12. Interestingly, trisomy 12 is also prevalent in germ cell tumors (GCTs). Here, we aimed to dissect the cellular and molecular implications of trisomy 12 in hPSCs. A genome-wide gene expression analysis revealed that trisomy 12 profoundly affects the global gene expression profile of hPSCs, inducing a transcriptional program very similar to that of CGTs. Direct comparison of the proliferation, replication, differentiation and apoptosis between diploid and aneuploid hPSCs revealed that trisomy 12 significantly increases the proliferation rate of hPSCs. Increased replication largely accounts for the increased proliferation observed, and may explain the selection advantage that trisomy 12 confers to hPSCs. A comparison of the tumors induced by diploid and aneuploid hPSCs further demonstrated that trisomy 12 increases the tumorigenicity of hPSCs, inducing transcriptionally-distinct teratomas, from which pluripotent cells can be recovered. Lastly, a chemical screen of 89 anticancer drugs against diploid and aneuploid hPSCs discovered that trisomy 12 raises the sensitivity of hPSCs to several replication inhibitors, suggesting that the increased proliferation and tumorigenicity of these aberrant cells also makes them more vulnerable, and might potentially be used for their selective elimination from culture. Together, our findings demonstrate the extensive effect of trisomy 12 on the gene expression signature and on the cellular behavior of hPSCs, and highlight the danger posed by this trisomy for the successful use of hPSCs in basic research and in regenerative medicine. Expression data from diploid and aneuoploid human pluripotent stem cells, teratomas derived from them, and pluripotent-like cells recovered from these teratomas total RNA was isolated from undifferentiated human pluripotent stem cells grown under standard human ES conditions, or from teratomas derived from them, or from ES-like cells recovered from these teratomas.
2014-09-01 | E-GEOD-51455 | biostudies-arrayexpress
Project description:Tissue for normal colonic stem cell isolation was obtained via colectomy from a colorectal cancer patient. It was shown that the resected tissue and the in vitro-cultured organoids grown from tissue-derived adult stem cells do not harbor chromosomal alterations. For that purpose, genomic DNA from resected mucosa or genomic DNA from adult stem cell-derived organoids grown in a 3-dimensional culture system was compared to white blood cell genomic DNA obtained from the same individual. Furthermore, in vitro organoids which were cultured and serially passaged for several weeks did not acquire chromosomal alterations. Analysis of chromosomal stability of colonic tissue or in vitro-cultured organoids via comparison with blood cells derived from the same individual.
2011-11-22 | E-GEOD-31256 | biostudies-arrayexpress
Project description:The gDNA of wild type (WT, Col-0), aur2-1 mutant (AAa), and WT trisomy 2 (AAA) were labeled and hybridized with Affymetrix Arabidopsis Tilling 1.0R arrays. The ratio of signal intensity of chromosomes in trisomy (AAa and AAA) to diploid (Col-0) were analyzed. The results indicated that the aur2-1 mutant was a tertiary trisomy (2n + 2L.3S).
2014-12-22 | GSE39844 | GEO
Project description:The whole-genome oligonucleotide microarray analysis of laser microdissected human colonic epithelial cells can contribute to determination of disease-specific expression alterations in colonic epithelial cells and to localize the origin the expression changes measured in whole biopsy samples. Keywords: whole genomic expression Total RNA was extracted from laser microdissected human colon epithelial cells and hybridized on Affymetrix HGU133 Plus 2.0 microarrays
2010-03-15 | E-GEOD-15960 | biostudies-arrayexpress
Project description:The whole-genome oligonucleotide microarray analysis of laser microdissected human colonic epithelial cells can contribute to determination of disease-specific expression alterations in colonic epithelial cells and to localize the origin the expression changes measured in whole biopsy samples. Keywords: whole genomic expression
2010-03-03 | GSE15960 | GEO
Project description:Karyotypic instability, including numerical and structural chromosomal aberrations, represents a distinct feature of multiple myeloma (MM). 40-50% of patients displayed hyperdiploidy, defined by recurrent trisomies of non-random chromosomes. To characterize hyperdiploid (H) and nonhyperdiploid (NH) MM molecularly, we analyzed the gene expression profiles of 66 primary tumors, and used FISH to investigate the major chromosomal alterations. The differential expression of 225 genes mainly involved in protein biosynthesis, transcriptional machinery and oxidative phosphorylation distinguished the 28 H-MM from the 38 NH-MM cases. The 204 upregulated genes in H-MM mapped mainly to the chromosomes involved in hyperdiploidy, and the29% up-regulated genes in NH-MM mapped to 16q. The identified transcriptional fingerprint was robustly validated on a publicly available gene expression dataset of 64 MM cases; and the global expression modulation of regions on the chromosomes involved in hyperdiploidy was verified using a self-developed non-parametric statistical method. We showed that H-MM could be further divided into two distinct molecular and transcriptional entities, characterized by the presence of trisomy 11 and 1q-extracopies/chromosome 13 deletion, respectively. Our data reinforce the importance of combining molecular cytogenetics and gene expression profiling to define a genomic framework for the study of MM pathogenesis and clinical management. Keywords: other
2007-01-01 | GSE6401 | GEO