Cited by 378Bioinformatics and Genomic NetworksViral-associated cancers and disordersCervical Cancer and HPV Research

Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins

Open access
Rozenblatt-Rosen, Orit, Deo, Rahul C., Padi, Megha, Adelmant, Guillaume, Calderwood, Michael A., Rolland, Thomas, Grace, Miranda, Dricot, Amélie +44 more·2012·Nature

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/nature11288

Cites

32 of 32 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

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
Venue
Nature
Published
2012-07
Volume
487
Issue
7408
Pages
491-495
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
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
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review