Supplementary Figure 3 from Insertional Mutagenesis in Mice Deficient for p15Ink4b, p16Ink4a, p21Cip1, and p27Kip1 Reveals Cancer Gene Interactions and Correlations with Tumor Phenotypes

Kool, Jaap; Uren, Anthony G.; Martins, Carla P.; Sie, Daoud; de Ridder, Jeroen; Turner, Geoffrey; van Uitert, Miranda; Matentzoglu, Konstantin; Lagcher, Wendy; Krimpenfort, Paul; Gadiot, Jules; Pritchard, Colin; Lenz, Jack; Lund, Anders H.; Jonkers, Jos; Rogers, Jane; Adams, David J.; Wessels, Lodewyk; Berns, Anton; van Lohuizen, Maarten

doi:10.1158/0008-5472.22385435.v1

00085472can092736-sup-sfi_g3.pdf (176.71 kB)

Supplementary Figure 3 from Insertional Mutagenesis in Mice Deficient for p15^Ink4b, p16^Ink4a, p21^Cip1, and p27^Kip1 Reveals Cancer Gene Interactions and Correlations with Tumor Phenotypes

journal contribution

posted on 2023-03-30, 19:53 authored by Jaap Kool, Anthony G. Uren, Carla P. Martins, Daoud Sie, Jeroen de Ridder, Geoffrey Turner, Miranda van Uitert, Konstantin Matentzoglu, Wendy Lagcher, Paul Krimpenfort, Jules Gadiot, Colin Pritchard, Jack Lenz, Anders H. Lund, Jos Jonkers, Jane Rogers, David J. Adams, Lodewyk Wessels, Anton Berns, Maarten van Lohuizen

Supplementary Figure 3 from Insertional Mutagenesis in Mice Deficient for p15^Ink4b, p16^Ink4a, p21^Cip1, and p27^Kip1 Reveals Cancer Gene Interactions and Correlations with Tumor Phenotypes

History

ARTICLE 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. Cancer Res; 70(2); 520–31

Usage metrics

Keywords

Carcinogenesis Animal models of carcinogenesis Mutagenesis Cell Cycle CDKs and CDK inhibitors Hematological Cancers Leukemias Preclinical Models Animal models of cancer Viral Oncogenesis Retroviruses

Licence

CC BY