| First Author | Verhagen MP | Year | 2024 |
| Journal | Nat Genet | Volume | 56 |
| Issue | 7 | Pages | 1456-1467 |
| PubMed ID | 38902475 | Mgi Jnum | J:358045 |
| Mgi Id | MGI:7778609 | Doi | 10.1038/s41588-024-01801-y |
| Citation | Verhagen MP, et al. (2024) Non-stem cell lineages as an alternative origin of intestinal tumorigenesis in the context of inflammation. Nat Genet 56(7):1456-1467 |
| abstractText | According to conventional views, colon cancer originates from stem cells. However, inflammation, a key risk factor for colon cancer, has been shown to suppress intestinal stemness. Here, we used Paneth cells as a model to assess the capacity of differentiated lineages to trigger tumorigenesis in the context of inflammation in mice. Upon inflammation, Paneth cell-specific Apc mutations led to intestinal tumors reminiscent not only of those arising in patients with inflammatory bowel disease, but also of a larger fraction of human sporadic colon cancers. The latter is possibly because of the inflammatory consequences of western-style dietary habits, a major colon cancer risk factor. Machine learning methods designed to predict the cell-of-origin of cancer from patient-derived tumor samples confirmed that, in a substantial fraction of sporadic cases, the origins of colon cancer reside in secretory lineages and not in stem cells. |
