Integrated genomic and function characterization of the 8q22 gain
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE19615 | GEO | 2010/01/05
SECONDARY ACCESSION(S): PRJNA122457
REPOSITORIES: GEO
Similar Datasets
Project description:We investigated the features of the genomic rearrangements in a cohort of 50 male individuals with proteolipid protein 1 (PLP1) copy number gain events who were ascertained with Pelizaeus-Merzbacher disease (PMD; MIM: 312080). Genomic rearrangements in PMD individuals with PLP1 copy number gain events were investigated by high-density customized array and breakpoint junction sequence analysis. Analysis of these data enabled the spectrum and relative distribution of the underlying genomic mutational signatures to be delineated. Genomic rearrangements in PMD individuals with PLP1 copy number gain events were investigated by high-density customized array and breakpoint junction sequence analysis.
2019-10-09 | GSE138542 | GEO
Project description:Purpose: To improve clinical outcome of gastric cancer patients, most emphasis is on improving therapeutic regimens, including more extensive surgery as well as (neo)adjuvant chemotherapy. The present study set out to identify, based on DNA copy number profiling, subgroups of patients with different clinical outcomes who thus would qualify for different therapy intensities. Experimental Design: DNA of 206 gastric cancer patients was isolated and analyzed by genome wide array comparative genomic hybridization. DNA copy number profiles were evaluated and correlated to lymph node status and survival. In addition, HSP90 protein expression was analyzed and correlated to survival in 290 gastric cancer patients. Results: Frequent (>20%) DNA copy number gains were observed on chromosomes 1p, 6p, 7p, 7q, 8q, 11q, 12q, 13q, 16p, 16q, 17q, 19p, 19q, 20p, 20q, 21q and 22q, and losses on chromosomes 4p, 4q, 6p, 6q, 9p, 13q and 21q. Lymph node negative gastric cancers showed significantly more losses on chromosomes 5q11.2-q35.1, 10q11.23-21.3 and 14q32.11-q32.33. In addition, losses on 5q11.2-q31.3 and 14q32.11-q32.33 were highly correlated to good clinical outcome, in both lymph node negative and positive gastric cancer patients. Loss of expression of HSP90, located on chromosome 14q32.2, correlated to good survival time. Conclusion: Genome wide DNA copy number profiling allows to identify a subgroup of gastric cancers, marked by losses on chromosomes 5q11.2-q31.3 and 14q32.11-q32.33 that have an excellent clinical outcome after surgery alone, and patients with these tumors are unlikely to benefit from additional intensified therapies. Possible biological mechanisms could involve loss of heat shock proteins, of which the coding genes are located at these chromosomal regions. 183 gastric adenocarcinomas
2012-05-09 | E-GEOD-26389 | biostudies-arrayexpress
Project description:Aneuploidy, defined as whole chromosome gain or loss, causes cellular stress but, paradoxically, is a frequent occurrence in cancers. Here, we investigate why around 50% of Ewing sarcomas, driven by the EWS-FLI1 fusion oncogene, harbor chromosome 8 gains. Expression of the EWS-FLI1 fusion in primary cells causes replication stress that can result in cellular senescence. Using an evolution approach, we show that trisomy 8 mitigates EWS-FLI1 induced replication stress through gain of a copy of RAD21. Low-level ectopic expression of RAD21 is sufficient to dampen replication stress and improve proliferation in EWS-FLI1 expressing cells. Conversely, deleting one copy in trisomy 8 cells largely neutralizes the fitness benefit of chromosome 8 gain and reduces tumorgenicity of an Ewing sarcoma cancer cell line in soft agar assays. We propose that RAD21 promotes tumorigenesis through single gene copy gain. Such genes may explain some recurrent aneuploidies in cancer.
2021-04-22 | GSE125529 | GEO
Project description:Chromosomal structural mutations play an important role in determining the transcriptional landscape of human breast cancers. We determined that pro-oncogenic and anti-oncogenic genes are clustered throughout the genome and that these clusters coincide with regions of segmental amplification and deletion. We constructed detailed structural mutation maps of representative breast cancers and found that tandem duplications appear to nucleate regions for amplification. Subsequent rearrangements link distant pro-oncogenic elements for co-amplification, and are associated with loss of tumor suppressors. We show that genes engaged in co-amplifications or conjoint deletions on 17q and 8q have pro-growth effects that are additive in nature. Our results suggest structural mutations efficiently orchestrate the gain and loss of cancer gene cassettes that engage many oncogenic pathways simultaneously. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from fresh-frozen breast tumors with >80% tumor cell content and their paired peripheral blood samples. Copy number analysis of the SNP arrays was done using the copy number pipeline implemented into Partek software version 6.5
2013-06-29 | E-GEOD-48377 | biostudies-arrayexpress
Project description:Neoadjuvant chemotherapy (NAC) has been of recent interest as an alternative to upfront surgery followed by adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC). However, a subset of patients does not respond to NAC and may have been better managed by upfront surgery. Hence, there is an unmet need for accurate biomarkers for predicting NAC response in PDAC. This project aimed to identify upregulated proteins in tumor tissue from poor- and good-NAC responders.
2020-04-16 | PXD017051 | Pride
Project description:To characterize the genetic alterations that instigate hepatitis C virus-induced hepatocellular carcinoma (HCC), we conducted an integrative genomic analysis of 103 HCCs. Most tumors harbored 1q gain, 8q gain or 8p loss, with occasional alterations in 13 additional chromosome arms. In addition to amplifications at 11q13 in 6 tumors, 4 tumors harbored focal gains at 6p21 incorporating VEGFA, which were confirmed in 4 of 113 HCC in an independent validation set. Strikingly, this locus overlapped with copy gains in 4 of 371 lung adenocarcinomas. Overexpression of VEGFA via 6p21 gain suggested a cell-nonautonomous mechanism of oncogene activation. Hierarchical clustering of gene expression among 91 tumors identified 5 classes, including ‘Wnt-CTNNB1’, ‘proliferation’ and ‘interferon-related’ gene classes. We also discovered a novel class defined by polysomy of chromosome 7, gains of which were associated with early tumor recurrence after resection. These findings reveal key alterations in HCC pathogenesis and implicate potential therapeutic targets. Keywords: disease state analysis
2008-06-22 | GSE9845 | GEO
Project description:To characterize the genetic alterations that instigate hepatitis C virus-induced hepatocellular carcinoma (HCC), we conducted an integrative genomic analysis of 103 HCCs. Most tumors harbored 1q gain, 8q gain or 8p loss, with occasional alterations in 13 additional chromosome arms. In addition to amplifications at 11q13 in 6 tumors, 4 tumors harbored focal gains at 6p21 incorporating VEGFA, which were confirmed in 4 of 113 HCC in an independent validation set. Strikingly, this locus overlapped with copy gains in 4 of 371 lung adenocarcinomas. Overexpression of VEGFA via 6p21 gain suggested a cell-nonautonomous mechanism of oncogene activation. Hierarchical clustering of gene expression among 91 tumors identified 5 classes, including ‘Wnt-CTNNB1’, ‘proliferation’ and ‘interferon-related’ gene classes. We also discovered a novel class defined by polysomy of chromosome 7, gains of which were associated with early tumor recurrence after resection. These findings reveal key alterations in HCC pathogenesis and implicate potential therapeutic targets. Keywords: disease state analysis
2008-06-22 | GSE9843 | GEO
Project description:To characterize the genetic alterations that instigate hepatitis C virus-induced hepatocellular carcinoma (HCC), we conducted an integrative genomic analysis of 103 HCCs. Most tumors harbored 1q gain, 8q gain or 8p loss, with occasional alterations in 13 additional chromosome arms. In addition to amplifications at 11q13 in 6 tumors, 4 tumors harbored focal gains at 6p21 incorporating VEGFA, which were confirmed in 4 of 113 HCC in an independent validation set. Strikingly, this locus overlapped with copy gains in 4 of 371 lung adenocarcinomas. Overexpression of VEGFA via 6p21 gain suggested a cell-nonautonomous mechanism of oncogene activation. Hierarchical clustering of gene expression among 91 tumors identified 5 classes, including 'Wnt-CTNNB1', 'proliferation' and 'nterferon-related' gene classes. We also discovered a novel class defined by polysomy of chromosome 7, gains of which were associated with early tumor recurrence after resection. These findings reveal key alterations in HCC pathogenesis and implicate potential therapeutic targets. Experiment Overall Design: 91 hepatocellular carcinomas were obtained at the time of surgical resection or orthotopic transplantation.
2008-10-25 | E-GEOD-9843 | biostudies-arrayexpress
Project description:To characterize the genetic alterations that instigate hepatitis C virus-induced hepatocellular carcinoma (HCC), we conducted an integrative genomic analysis of 103 HCCs. Most tumors harbored 1q gain, 8q gain or 8p loss, with occasional alterations in 13 additional chromosome arms. In addition to amplifications at 11q13 in 6 tumors, 4 tumors harbored focal gains at 6p21 incorporating VEGFA, which were confirmed in 4 of 113 HCC in an independent validation set. Strikingly, this locus overlapped with copy gains in 4 of 371 lung adenocarcinomas. Overexpression of VEGFA via 6p21 gain suggested a cell-nonautonomous mechanism of oncogene activation. Hierarchical clustering of gene expression among 91 tumors identified 5 classes, including ‘Wnt-CTNNB1’, ‘proliferation’ and ‘interferon-related’ gene classes. We also discovered a novel class defined by polysomy of chromosome 7, gains of which were associated with early tumor recurrence after resection. These findings reveal key alterations in HCC pathogenesis and implicate potential therapeutic targets. Keywords: disease state analysis 103 hepatocellular carcinomas and 95 adjacent cirrhotic, non-tumoral liver tissue were obtained at the time of surgical resection of orthotopic transplantation.
2008-06-21 | E-GEOD-9845 | biostudies-arrayexpress
Project description:Somatic mosaicism is a known cause of neurological disorders, including developmental brain malformations and epilepsy. Brain mosaic copy number gain of chromosome 1q is associated with cortical malformations, early-onset epilepsy, and developmental delay. Pathogenic brain mosaicism is traditionally attributed to post-zygotic genetic alterations arising in a neural progenitor cell during fetal development. However, in our cohort, in at least five of six patients with brain mosaic copy number gain of chromosome 1q, the alteration occurred pre-conception. We observed a third non-constitutive, but parentally-derived, haplotype for chromosome 1q in patient brain tissue, demonstrating that the copy number alteration occurred in a gamete pre-conception. The altered cells had no representation in parental buccal or proband blood or buccal samples, but were prominently observed in proband brain tissue, suggesting the copy number gain was lost in most cell lineages during embryonic development. Single-nuclei genotyping coupled with gene expression profiling revealed a strong enrichment of the chromosome 1q gain in astrocytes, which correlated with the unusual finding of hyaline astrocytic inclusions in all six cases.
2023-09-08 | GSE221849 | GEO