Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 2005 May 10;102(19):6960-5. Epub 2005 May 3.

Polyclonality of familial murine adenomas: analyses of mouse chimeras with low tumor multiplicity suggest short-range interactions.

Author information

  • 1McArdle Laboratory for Cancer Research, Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53706, USA.

Abstract

In previous studies demonstrating the polyclonal structure of familial intestinal adenomas, high tumor multiplicity made it difficult to eliminate the possibility that polyclonality arose by the random collision of distinct initiated clones as opposed to some form of clonal interaction. We sought to test further the random collision hypothesis. Chimeric mice carrying the multiple intestinal neoplasia (Min) mutation of the adenomatous polyposis coli gene (Apc) and homozygous for the tumor resistance allele of the Mom1 locus were established. These chimeras also display a strong propensity for tumors of polyclonal structure, despite their markedly reduced tumor multiplicity. Considering tumor sizes and multiplicities, the observed fraction of overtly polyclonal heterotypic adenomas was significantly higher than predicted by the random collision hypothesis. This finding supports models of polyclonality involving interaction among multiple initiated clones. The extent of clonal interaction was assessed by statistical analyses that relate the observed frequency of overtly polyclonal heterotypic tumors to the geometry of the chimeric patches and the pattern of underlying crypts. These statistical calculations indicate that the familial adenomas of the Apc(Min/+) mouse may commonly form through interactions between clones as close as 1-2 crypt diameters apart.

PMID:
15870186
[PubMed - indexed for MEDLINE]
PMCID:
PMC1100801
Free PMC Article

Images from this publication.See all images (4)Free text

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk