A cancer rainbow mouse for visualizing the functional genomics of oncogenic clonal expansion.

Journal Article (Journal Article)

Field cancerization is a premalignant process marked by clones of oncogenic mutations spreading through the epithelium. The timescales of intestinal field cancerization can be variable and the mechanisms driving the rapid spread of oncogenic clones are unknown. Here we use a Cancer rainbow (Crainbow) modelling system for fluorescently barcoding somatic mutations and directly visualizing the clonal expansion and spread of oncogenes. Crainbow shows that mutations of ß-catenin (Ctnnb1) within the intestinal stem cell results in widespread expansion of oncogenes during perinatal development but not in adults. In contrast, mutations that extrinsically disrupt the stem cell microenvironment can spread in adult intestine without delay. We observe the rapid spread of premalignant clones in Crainbow mice expressing oncogenic Rspondin-3 (RSPO3), which occurs by increasing crypt fission and inhibiting crypt fixation. Crainbow modelling provides insight into how somatic mutations rapidly spread and a plausible mechanism for predetermining the intratumor heterogeneity found in colon cancers.

Full Text

Duke Authors

Cited Authors

  • Boone, PG; Rochelle, LK; Ginzel, JD; Lubkov, V; Roberts, WL; Nicholls, PJ; Bock, C; Flowers, ML; von Furstenberg, RJ; Stripp, BR; Agarwal, P; Borowsky, AD; Cardiff, RD; Barak, LS; Caron, MG; Lyerly, HK; Snyder, JC

Published Date

  • December 2, 2019

Published In

Volume / Issue

  • 10 / 1

Start / End Page

  • 5490 -

PubMed ID

  • 31792216

Pubmed Central ID

  • PMC6889384

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-019-13330-y


  • eng

Conference Location

  • England