Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Nat Genet. 2011 Nov 6;43(12):1202-9. doi: 10.1038/ng.990.

Insertional mutagenesis identifies multiple networks of cooperating genes driving intestinal tumorigenesis.

Author information

  • 1Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, UK.

Abstract

The evolution of colorectal cancer suggests the involvement of many genes. To identify new drivers of intestinal cancer, we performed insertional mutagenesis using the Sleeping Beauty transposon system in mice carrying germline or somatic Apc mutations. By analyzing common insertion sites (CISs) isolated from 446 tumors, we identified many hundreds of candidate cancer drivers. Comparison to human data sets suggested that 234 CIS-targeted genes are also dysregulated in human colorectal cancers. In addition, we found 183 CIS-containing genes that are candidate Wnt targets and showed that 20 CISs-containing genes are newly discovered modifiers of canonical Wnt signaling. We also identified mutations associated with a subset of tumors containing an expanded number of Paneth cells, a hallmark of deregulated Wnt signaling, and genes associated with more severe dysplasia included those encoding members of the FGF signaling cascade. Some 70 genes had co-occurrence of CIS pairs, clustering into 38 sub-networks that may regulate tumor development.

PMID:
22057237
[PubMed - indexed for MEDLINE]
PMCID:
PMC3233530
Free PMC Article

Images from this publication.See all images (5)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Nature Publishing Group Icon for PubMed Central Icon for Faculty of 1000
    Loading ...
    Write to the Help Desk