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Cited by 347Genomic variations and chromosomal abnormalitiesGene expression and cancer classificationCancer Genomics and Diagnostics

Gene expression analysis identifies global gene dosage sensitivity in cancer

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Fehrmann, Rudolf S N, Karjalainen, Juha M, Krajewska, Małgorzata, Westra, Harm-Jan, Maloney, David, Simeonov, Anton, Pers, Tune H, Hirschhorn, Joel N +8 more·2015·Nature Genetics
DOI 10.1038/ng.3173
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Abstract

Many cancer-associated somatic copy number alterations (SCNAs) are known. Currently, one of the challenges is to identify the molecular downstream effects of these variants. Although several SCNAs are known to change gene expression levels, it is not clear whether each individual SCNA affects gene expression. We reanalyzed 77,840 expression profiles and observed a limited set of 'transcriptional components' that describe well-known biology, explain the vast majority of variation in gene expression and enable us to predict the biological function of genes. On correcting expression profiles for these components, we observed that the residual expression levels (in 'functional genomic mRNA' profiling) correlated strongly with copy number. DNA copy number correlated positively with expression levels for 99% of all abundantly expressed human genes, indicating global gene dosage sensitivity. By applying this method to 16,172 patient-derived tumor samples, we replicated many loci with aberrant copy numbers and identified recurrently disrupted genes in genomically unstable cancers.

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Crossref · 10.1038/ng.3173

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  • Signatures unique to the cancer had a strong signal for genes duplicated in the cancer, suggesting that identified profiles reflect the oncogenic events in the genome.

    “Both of these studies demonstrated that signatures unique to the cancer had a strong signal for genes duplicated in the cancer [137, 138], as is common in cancers, suggesting that identified profiles reflect the oncogenic events in the genome.”

    From Gene co-expression analysis for functional classification and gene–disease predictions (2017) · cites this paper as [138]

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References 34 · Cited by 347

Authors
Fehrmann, R. S. N., Karjalainen, J. M., Krajewska, M., Westra, H.-J., Maloney, D., Simeonov, A., Pers, T. H., Hirschhorn, J. N., Jansen, R. C., Schultes, E. A., van Haagen, H. H. H. B. M., de Vries, E. G. E., te Meerman, G. J., Wijmenga, C., van Vugt, M. A. T. M., & Franke, L.
Affiliations
  • University Medical Center Groningen (NL)
  • National Institutes of Health (US)
  • Broad Institute (US)
  • University of Groningen (NL)
  • Leiden University (NL)
Corresponding author
  • Fehrmann, Rudolf S N
  • Franke, Lude
ORCID
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
2015-01-12
Volume
47
Issue
2
Pages
115-125
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
DOI
10.1038/ng.3173
OpenAlex
W2072789685
Cited by
347
References
34
Citations by year
2026: 20 · 2025: 20 · 2024: 26 · 2023: 24 · 2022: 23 · 2021: 29 · 2020: 38 · 2019: 40 · 2018: 26 · 2017: 41 · 2016: 43 · 2015: 17
FWCI
29.30
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
Funders
Lundbeckfonden (R190 2014-3904)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Keywords
gene dosage sensitivity, copy number alterations, somatic copy number alterations, gene expression, cancer, therapeutic target, gene function prediction, tumor samples
MeSH terms
Humans, Neoplasms, RNA, Messenger, RNA, Neoplasm, Gene Expression Regulation, Neoplastic, Gene Dosage, Gene Expression Profiling, Genomics, Gene Regulatory Networks, Comparative Genomic Hybridization, Genetic Loci, DNA Copy Number Variations, Transcriptome

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