Published
online before print June 11, 2002, 10.1073/pnas.132275099
Proc. Natl. Acad. Sci. USA, vol. 99, no. 13, pp. 8927-8931 (June
25, 2002).
http://www.pnas.org/cgi/doi/10.1073/pnas.132275099
"Intestinal Adenomas Can Develop with a Stable Karyotype
and Stable Microsatellites".
Kevin M. Haigis 1, James G. Caya2 , Mark Reichelderfer
3, and William F. Dove 1, @
1 McArdle Laboratory for Cancer Research and Laboratory
of Genetics, University of Wisconsin, 1400 University Avenue, Madison,
WI 53706;
2 Department of Pathology and Laboratory Medicine, University
of Wisconsin Medical School, DM238 Veterans Administration Hospital, 2500
Overlook Terrace, Madison, WI 53705; and
3 Department of Medicine, University of Wisconsin Medical
School, BX5124 Clinical Science Center, 600 Highland Avenue, Madison, WI
53792
@ To whom reprint requests should be addressed. E-mail:
dove@oncology.wisc.edu
Abstract:
Loss of function of the adenomatous polyposis coli (APC)/Apc
tumor suppressor gene occurs early in the etiology of intestinal cancer
in mammals. In human colonic tumors, genomic instability is proposed to
be associated with tumor initiation by inducing loss of APC function.
We have used a mouse model of inherited intestinal cancer (ApcMin/+,
Min/+) to analyze the earliest stages of tumorigenesis in
this organ. We find that tumors from C57BL/6 Min/+ mice have a stable
karyotype and stable microsatellites. In contrast to previous claims, we
find that homozygosity for the Min allele of Apc in tumors
can proceed by homologous somatic recombination. Further, our analysis
of early, benign human colorectal adenomas failed to reveal any evidence
for generalized chromosomal or microsatellite instability. These results
cast doubt on the hypothesis that either of these forms of genomic instability
is necessary for the initial development of colorectal adenomas. We contrast
our analysis of autochthonous primary tumors to other studies involving
xenografts or cultured
cells.
Additional References:
1. Meisner LF, and Frenster JH, "In
Vivo Evolution within Radiation-Induced Clones of Human Lymphocytes".
2. Frenster JH, "Ultrastructural Probes of Active
DNA Sites, and the RNA Activators of DNA".
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