Abstract
Originalsprog | Engelsk |
---|---|
Tidsskrift | Cancer Research |
Vol/bind | 70 |
Udgave nummer | 2 |
Sider (fra-til) | 520-31 |
Antal sider | 11 |
DOI | |
Status | Udgivet - 2010 |
Adgang til dokumentet
Citationsformater
- APA
- Standard
- Harvard
- Vancouver
- Author
- BIBTEX
- RIS
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.
I: Cancer Research, Bind 70, Nr. 2, 2010, s. 520-31.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
TY - JOUR
T1 - Insertional mutagenesis in mice deficient for p15Ink4b, p16Ink4a, p21Cip1, and p27Kip1 reveals cancer gene interactions and correlations with tumor phenotypes
AU - Kool, Jaap
AU - Uren, Anthony G
AU - Martins, Carla P
AU - Sie, Daoud
AU - de Ridder, Jeroen
AU - Turner, Geoffrey
AU - van Uitert, Miranda
AU - Matentzoglu, Konstantin
AU - Lagcher, Wendy
AU - Krimpenfort, Paul
AU - Gadiot, Jules
AU - Pritchard, Colin
AU - Lenz, Jack
AU - Lund, Anders H
AU - Jonkers, Jos
AU - Rogers, Jane
AU - Adams, David J
AU - Wessels, Lodewyk
AU - Berns, Anton
AU - van Lohuizen, Maarten
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
U2 - 10.1158/0008-5472.CAN-09-2736
DO - 10.1158/0008-5472.CAN-09-2736
M3 - Journal article
C2 - 20068150
VL - 70
SP - 520
EP - 531
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 2
ER -