The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins
Open accessAbstract
Genotypic differences greatly influence susceptibility and resistance to disease. Understanding genotype-phenotype relationships requires that phenotypes be viewed as manifestations of network properties, rather than simply as the result of individual genomic variations. Genome sequencing efforts have identified numerous germline mutations, and large numbers of somatic genomic alterations, associated with a predisposition to cancer. However, it remains difficult to distinguish background, or 'passenger', cancer mutations from causal, or 'driver', mutations in these data sets. Human viruses intrinsically depend on their host cell during the course of infection and can elicit pathological phenotypes similar to those arising from mutations. Here we test the hypothesis that genomic variations and tumour viruses may cause cancer through related mechanisms, by systematically examining host interactome and transcriptome network perturbations caused by DNA tumour virus proteins. The resulting integrated viral perturbation data reflects rewiring of the host cell networks, and highlights pathways, such as Notch signalling and apoptosis, that go awry in cancer. We show that systematic analyses of host targets of viral proteins can identify cancer genes with a success rate on a par with their identification through functional genomics and large-scale cataloguing of tumour mutations. Together, these complementary approaches increase the specificity of cancer gene identification. Combining systems-level studies of pathogen-encoded gene products with genomic approaches will facilitate the prioritization of cancer-causing driver genes to advance the understanding of the genetic basis of human cancer.
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“Nearly 3800 virus–host protein interactions were identified by Rozenblatt-Rosen et al. in a single study of DNA tumor virus proteins from four viruses, HPV, EBV, adenovirus Ad5, and human polyomavirus [91].”
From Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection (2016) · cites this paper as [91]
In the citing paper
“the cellular transcriptional regulators cAMP-response element binding protein and EP300 were only found to associate with the E6 oncoprotein of HPV from cutaneous subtypes and not mucosal subtypes.”
From Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection (2016) · cites this paper as [91]
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“The identified associations stemmed from 54 viral and 1079 host proteins that pointed to viral subtype-specificity in interactions.”
From Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection (2016) · cites this paper as [91]
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Metadata
- Authors
- Rozenblatt-Rosen, O., Deo, R. C., Padi, M., Adelmant, G., Calderwood, M. A., Rolland, T., Grace, M., Dricot, A., Askenazi, M., Tavares, M., Pevzner, S. J., Abderazzaq, F., Byrdsong, D., Carvunis, A.-R., Chen, A. A., Cheng, J., Correll, M., Duarte, M., Fan, C., Feltkamp, M. C., Ficarro, S. B., Franchi, R., Garg, B. K., Gulbahce, N., Hao, T., Holthaus, A. M., James, R., Korkhin, A., Litovchick, L., Mar, J. C., Pak, T. R., Rabello, S., Rubio, R., Shen, Y., Singh, S., Spangle, J. M., Tasan, M., Wanamaker, S., Webber, J. T., Roecklein-Canfield, J., Johannsen, E., Barabási, A.-L., Beroukhim, R., Kieff, E., Cusick, M. E., Hill, D. E., Münger, K., Marto, J. A., Quackenbush, J., Roth, F. P., DeCaprio, J. A., & Vidal, M.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Boston University (US)
- Dana-Farber Cancer Institute (US)
- Leiden University Medical Center (NL)
- Simmons University (US)
- Northeastern University (US)
- Mount Sinai Hospital (CA)
- Broad Institute (US)
- Corresponding author
- Marto, Jarrod A.
- Quackenbush, John
- Roth, Frederick P.
- DeCaprio, James A.
- Vidal, Marc
- ORCID
- Deo, Rahul C.
- Padi, Megha
- Adelmant, Guillaume
- Calderwood, Michael A.
- Rolland, Thomas
- Askenazi, Manor
- Carvunis, Anne-Ruxandra
- Chen, Alyce A.
- Cheng, Jingwei
- Feltkamp, Mariet C.
- Ficarro, Scott B.
- Gulbahce, Natali
- Hao, Tong
- Litovchick, Larisa
- Mar, Jessica C.
- Pak, Theodore R.
- Spangle, Jennifer M.
- Wanamaker, Shelly
- Webber, James T.
- Johannsen, Eric
- Beroukhim, Rameen
- Hill, David E.
- Münger, Karl
- Marto, Jarrod A.
- Quackenbush, John
- Roth, Frederick P.
- DeCaprio, James A.
- Vidal, Marc
- Venue
- Nature
- Published
- 2012-07
- Volume
- 487
- Issue
- 7408
- Pages
- 491-495
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3408847
- OpenAlex
- W2085540051
- Cited by
- 378
- References
- 32
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 18 · 2023: 14 · 2022: 18 · 2021: 24 · 2020: 32 · 2019: 24 · 2018: 31 · 2017: 31 · 2016: 31 · 2015: 36 · 2014: 43 · 2013: 42 · 2012: 16
- FWCI
- 17.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (K08HL098361, T32HL007208)
- National Human Genome Research Institute (R01HG001715, K25HG006031, P50HG004233)
- National Cancer Institute (R01CA081135, R01CA093804, P01CA050661, R01CA047006, R01CA085180, K08CA122833, R01CA131354, R01CA066980, R01CA063113, U01CA141583)
- National Institute of General Medical Sciences (F32GM095284)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Keywords
- cancer driver genes, DNA tumor viruses, human papillomavirus, Epstein-Barr virus, adenovirus, polyomavirus, Notch signaling, apoptosis, passenger mutations, genotype-phenotype correlation, host-virus interaction
- MeSH terms
- Adenoviridae, Herpesvirus 4, Human, Humans, Neoplasms, Oncogenic Viruses, Polyomavirus, Viral Proteins, Signal Transduction, Genome, Human, Gene Expression Regulation, Neoplastic, Open Reading Frames, Two-Hybrid System Techniques, Gene Expression Profiling, Papillomaviridae, Receptors, Notch, Genes, Neoplasm, Host-Pathogen Interactions
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