Abstract:
BACKGROUND:Intra-tumor heterogeneity stems from genetic, epigenetic, functional, and environmental differences among tumor cells. A major source of genetic heterogeneity comes from DNA sequence differences and/or whole chromosome and focal copy number variations (CNVs). Whole chromosome CNVs are caused by chromosomal instability (CIN) that is defined by a persistently high rate of chromosome mis-segregation. Accordingly, CIN causes constantly changing karyotypes that result in extensive cell-to-cell genetic heterogeneity. How the genetic heterogeneity caused by CIN influences gene expression in individual cells remains unknown. METHODS:We performed single-cell RNA sequencing on a chromosomally unstable glioblastoma cancer stem cell (CSC) line and a control normal, diploid neural stem cell (NSC) line to investigate the impact of CNV due to CIN on gene expression. From the gene expression data, we computationally inferred large-scale CNVs in single cells. Also, we performed copy number adjusted differential gene expression analysis between NSCs and glioblastoma CSCs to identify copy number dependent and independent differentially expressed genes. RESULTS:Here, we demonstrate that gene expression across large genomic regions scales proportionally to whole chromosome copy number in chromosomally unstable CSCs. Also, we show that the differential expression of most genes between normal NSCs and glioblastoma CSCs is largely accounted for by copy number alterations. However, we identify 269 genes whose differential expression in glioblastoma CSCs relative to normal NSCs is independent of copy number. Moreover, a gene signature derived from the subset of genes that are differential expressed independent of copy number in glioblastoma CSCs correlates with tumor grade and is prognostic for patient survival. CONCLUSIONS:These results demonstrate that CIN is directly responsible for gene expression changes and contributes to both genetic and transcriptional heterogeneity among glioblastoma CSCs. These results also demonstrate that the expression of some genes is buffered against changes in copy number, thus preserving some consistency in gene expression levels from cell-to-cell despite the continuous change in karyotype driven by CIN. Importantly, a gene signature derived from the subset of genes whose expression is buffered against copy number alterations correlates with tumor grade and is prognostic for patient survival that could facilitate patient diagnosis and treatment.
journal_name
BMC Med Genomicsjournal_title
BMC medical genomicsauthors
Zhao Y,Carter R,Natarajan S,Varn FS,Compton DA,Gawad C,Cheng C,Godek KMdoi
10.1186/s12920-019-0532-5subject
Has Abstractpub_date
2019-05-31 00:00:00pages
79issue
1issn
1755-8794pii
10.1186/s12920-019-0532-5journal_volume
12pub_type
杂志文章abstract:BACKGROUND:Since it is assumed that genetic interactions play an important role in understanding the mechanisms of complex diseases, different statistical approaches have been suggested in recent years for this task. One interesting approach is the entropy-based IGENT method by Kwon et al. that promises an efficient de...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-020-0703-4
更新日期:2020-04-23 00:00:00
abstract:BACKGROUND:While most pediatric sarcomas respond to front-line therapy, some bone sarcomas do not show radiographic response like soft-tissue sarcomas (rhabdomyosarccomas) but do show 90% necrosis. Though, new therapies are urgently needed to improve survival and quality of life in pediatric patients with sarcomas. Com...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-018-0456-5
更新日期:2019-01-31 00:00:00
abstract:BACKGROUND:The right dataset is essential to obtain the right insights in data science; therefore, it is important for data scientists to have a good understanding of the availability of relevant datasets as well as the content, structure, and existing analyses of these datasets. While a number of efforts are underway ...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-018-0411-5
更新日期:2018-11-20 00:00:00
abstract:BACKGROUND:Cardiac pathological hypertrophy is associated with a significantly increased risk of coronary heart disease and has been observed in diabetic patients treated with rosiglitazone whereas most published studies do not suggest a similar increase in risk of cardiovascular events in pioglitazone-treated diabetic...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-7-35
更新日期:2014-06-17 00:00:00
abstract:BACKGROUND:Preterm birth (PTB), defined as infant delivery before 37 weeks of completed gestation, results from the interaction of both genetic and environmental components and constitutes a complex multifactorial syndrome. Transcriptome analysis of PTB has proven challenging because of the multiple causes of PTB and t...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-019-0498-3
更新日期:2019-04-01 00:00:00
abstract:BACKGROUND:Cytokine-induced killer (CIK) cells are an emerging approach of cancer treatment. Our previous study have shown that CIK cells stimulated with combination of IL-2 and IL-15 displayed improved proliferation capacity and tumor cytotoxicity. However, the mechanisms of CIK cell proliferation and acquisition of c...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-7-49
更新日期:2014-08-09 00:00:00
abstract:BACKGROUND:Gulf War Illness (GWI) is a complex multi-symptom disorder that affects up to one in three veterans of this 1991 conflict and for which no effective treatment has been found. Discovering novel treatment strategies for such a complex chronic illness is extremely expensive, carries a high probability of failur...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-015-0111-3
更新日期:2015-07-09 00:00:00
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journal_title:BMC medical genomics
pub_type: 杂志文章,多中心研究
doi:10.1186/s12920-015-0091-3
更新日期:2015-05-06 00:00:00
abstract:BACKGROUND:Breast cancer comprises multiple tumor entities associated with different biological features and clinical behaviors, making individualized medicine a powerful tool to bring the right drug to the right patient. Next generation sequencing of RNA (RNA-Seq) is a suitable method to detect targets for individuali...
journal_title:BMC medical genomics
pub_type: 杂志文章
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journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-3-8
更新日期:2010-03-16 00:00:00
abstract:BACKGROUND:Alterations in gene expression in peripheral blood cells have been shown to be sensitive to the presence and extent of coronary artery disease (CAD). A non-invasive blood test that could reliably assess obstructive CAD likelihood would have diagnostic utility. RESULTS:Microarray analysis of RNA samples from...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-4-26
更新日期:2011-03-28 00:00:00
abstract:BACKGROUND:Single nucleotide variants account for approximately 90% of all known pathogenic variants responsible for human diseases. Recently discovered CRISPR/Cas9 base editors can correct individual nucleotides without cutting DNA and inducing double-stranded breaks. We aimed to find all possible pathogenic variants ...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-020-00735-8
更新日期:2020-09-18 00:00:00
abstract:BACKGROUND:The noninvasive prenatal diagnosis procedures that are currently used to detect genetic diseases do not achieve desirable levels of sensitivity and specificity. Recently, fetal methylated DNA biomarkers in maternal peripheral blood have been explored for the noninvasive prenatal detection of genetic disorder...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-5-26
更新日期:2012-06-18 00:00:00
abstract:BACKGROUND:Loss of heterozygosity (LOH) is a common genetic event in cancer development, and is known to be involved in the somatic loss of wild-type alleles in many inherited cancer syndromes. The wider involvement of LOH in cancer is assumed to relate to unmasking a somatically mutated tumour suppressor gene through ...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-015-0123-z
更新日期:2015-08-01 00:00:00
abstract:BACKGROUND:Cancer cells are characterized by massive dysegulation of physiological cell functions with considerable disruption of transcriptional regulation. Genome-wide transcriptome profiling can be utilized for early detection and molecular classification of cancers. Accurate discrimination of functionally different...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-4-53
更新日期:2011-06-30 00:00:00
abstract:BACKGROUND:Despite being caused by mutations in different genes, diseases in the same phenotypic series are clinically similar, as reported in Part I of this study. Here, in Part II, we hypothesized that the phenotypic series too might be clinically similar. Furthermore, on the assumption that gene mutations indirectly...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-020-00793-y
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journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-4-63
更新日期:2011-08-09 00:00:00
abstract:BACKGROUND:Germline mutations in the folliculin (FLCN) gene are associated with the development of Birt-Hogg-Dubé syndrome (BHDS), a disease characterized by papular skin lesions, a high occurrence of spontaneous pneumothorax, and the development of renal neoplasias. The majority of renal tumors that arise in BHDS-affe...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-3-59
更新日期:2010-12-16 00:00:00
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journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-017-0283-0
更新日期:2017-06-19 00:00:00
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journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-1-46
更新日期:2008-09-30 00:00:00
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pub_type: 杂志文章
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更新日期:2013-01-01 00:00:00
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journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-017-0252-7
更新日期:2017-03-09 00:00:00
abstract:BACKGROUND:A clinical overlap exists between mosaic Neurofibromatosis Type 2 and sporadic Schwannomatosis conditions. In these cases a molecular analysis of tumors is recommended for a proper genetic diagnostics. This analysis is challenged by the fact that schwannomas in both conditions bear a somatic double inactivat...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-015-0076-2
更新日期:2015-01-24 00:00:00
abstract:BACKGROUND:Microtia-atresia is characterized by abnormalities of the auricle (microtia) and aplasia or hypoplasia of the external auditory canal, often associated with middle ear abnormalities. To date, no causal genetic mutations or genes have been identified in microtia-atresia patients. METHODS:We designed a panel ...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-019-0475-x
更新日期:2019-01-28 00:00:00
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journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-1-35
更新日期:2008-08-11 00:00:00
abstract:BACKGROUND:Insulin resistance (IR) is accompanied by chronic low grade systemic inflammation, obesity, and deregulation of total body energy homeostasis. We induced inflammation in adipose and liver tissues in vitro in order to mimic inflammation in vivo with the aim to identify tissue-specific processes implicated in ...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-4-71
更新日期:2011-10-06 00:00:00
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journal_title:BMC medical genomics
pub_type: 杂志文章
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更新日期:2015-01-01 00:00:00
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journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-018-0384-4
更新日期:2018-08-20 00:00:00
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journal_title:BMC medical genomics
pub_type: 社论
doi:10.1186/s12920-018-0448-5
更新日期:2019-01-31 00:00:00