Insertional mutagenesis identifies multiple networks of co-operating genes driving intestinal tumorigenesis
The evolution of colorectal cancer suggests the involvement of many genes. We performed insertional mutagenesis with the Sleeping Beauty (SB) transposon system in mice carrying germline or somatic Apc mutation. Analysis of common insertion sites (CISs) isolated from 446 tumors revealed many hundreds...
Gespeichert in:
Veröffentlicht in: | Nature genetics 2011-11, Vol.43 (12), p.1202-1209 |
---|---|
Hauptverfasser: | , , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | The evolution of colorectal cancer suggests the involvement of many genes. We performed insertional mutagenesis with the
Sleeping Beauty
(SB) transposon system in mice carrying germline or somatic
Apc
mutation. Analysis of common insertion sites (CISs) isolated from 446 tumors revealed many hundreds of candidate cancer drivers. Comparison to human datasets suggested that 234 CIS genes are also deregulated in human colorectal cancers. 183 CIS genes are candidate Wnt targets, and 20 are shown to be novel modifiers of canonical Wnt signaling. We also identified gene 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 members of the FGF signaling cascade. Some 70 genes showed pairwise co-occurrence clustering into 38 sub-networks that may regulate tumor development. |
---|---|
ISSN: | 1061-4036 1546-1718 |
DOI: | 10.1038/ng.990 |