@article{b7c91c80253111df8ed1000ea68e967b,
title = "Insertional mutagenesis in mice deficient for p15Ink4b, p16Ink4a, p21Cip1, and p27Kip1 reveals cancer gene interactions and correlations with tumor phenotypes",
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.",
author = "Jaap Kool and Uren, {Anthony G} and Martins, {Carla P} and Daoud Sie and {de Ridder}, Jeroen and Geoffrey Turner and {van Uitert}, Miranda and Konstantin Matentzoglu and Wendy Lagcher and Paul Krimpenfort and Jules Gadiot and Colin Pritchard and Jack Lenz and Lund, {Anders H} and Jos Jonkers and Jane Rogers and Adams, {David J} and Lodewyk Wessels and Anton Berns and {van Lohuizen}, Maarten",
year = "2010",
doi = "10.1158/0008-5472.CAN-09-2736",
language = "English",
volume = "70",
pages = "520--31",
journal = "Cancer Research",
issn = "0576-6656",
publisher = "American Association for Cancer Research",
number = "2",
}