ArticleCancer research2010
Insertional mutagenesis in mice deficient for p15Ink4b, p16Ink4a, p21Cip1, and p27Kip1 reveals cancer gene interactions and correlations with tumor phenotypes.
Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- Article
- Forward and Reverse Genetics of B Cell Malignancies: From Insertional Mutagenesis to CRISPR-Cas.Frontiers in immunology · 2021Review
- Subclonal mutation selection in mouse lymphomagenesis identifies known cancer loci and suggests novel candidates.Nature communications · 2018Article
- Ribosomal protein L23 negatively regulates cellular apoptosis via the RPL23/Miz-1/c-Myc circuit in higher-risk myelodysplastic syndrome.Scientific reports · 2017Article
- Gamma-Retrovirus Integration Marks Cell Type-Specific Cancer Genes: A Novel Profiling Tool in Cancer Genomics.PloS one · 2016Article
- 3D hotspots of recurrent retroviral insertions reveal long-range interactions with cancer genes.Nature communications · 2015Article
- Plac8 links oncogenic mutations to regulation of autophagy and is critical to pancreatic cancer progression.Cell reports · 2014Article
- Chromatin landscapes of retroviral and transposon integration profiles.PLoS genetics · 2014Article
- Insertional mutagenesis and deep profiling reveals gene hierarchies and a Myc/p53-dependent bottleneck in lymphomagenesis.PLoS genetics · 2014Article
- Deregulated Nras expression in knock-in animals harboring a gammaretroviral long terminal repeat at the Nras/Csde1 locus.PloS one · 2013Article
- Analysis of tumor heterogeneity and cancer gene networks using deep sequencing of MMTV-induced mouse mammary tumors.PloS one · 2013Article
- Profibrotic role of miR-154 in pulmonary fibrosis.American journal of respiratory cell and molecular biology · 2012Article
- Insights into Assessing the Genetics of Endometriosis.Current obstetrics and gynecology reports · 2012Article
- Cyclin dependent kinase inhibitors differentially modulate synergistic cytokine responsiveness of hematopoietic progenitor cells.Stem cells and development · 2012Article
- High-throughput semiquantitative analysis of insertional mutations in heterogeneous tumors.Genome research · 2011Article
- Review
- A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese.Nature genetics · 2010Article
- Applications of DNA integrating elements: Facing the bias bully.Mobile genetic elementsReview
- Mouse models of cancer as biological filters for complex genomic data.Disease models & mechanismsArticle
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 3 countries.
Funding
Abstract
The cyclin dependent kinase (CDK) inhibitors p15, p16, p21, and p27 are frequently deleted, silenced, or downregulated in many malignancies. Inactivation of CDK inhibitors predisposes mice to tumor development, showing that these genes function as tumor suppressors. Here, we describe high-throughput murine leukemia virus insertional mutagenesis screens in mice that are deficient for one or two CDK inhibitors. We retrieved 9,117 retroviral insertions from 476 lymphomas to define hundreds of loci that are mutated more frequently than expected by chance. Many of these loci are skewed toward a specific genetic context of predisposing germline and somatic mutations. We also found associations between these loci with gender, age of tumor onset, and lymphocyte lineage (B or T cell). Comparison of retroviral insertion sites with single nucleotide polymorphisms associated with chronic lymphocytic leukemia revealed a significant overlap between the datasets. Together, our findings highlight the importance of genetic context within large-scale mutation detection studies, and they show a novel use for insertional mutagenesis data in prioritizing disease-associated genes that emerge from genome-wide association studies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.