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Intestinal adenomas can develop with a stable karyotype and stable microsatellites
Kevin M Haigis1, James G Caya, Mark Reichelderfer
1McArdle Laboratory for Cancer Research and Laboratory of Genetics, University of Wisconsin, 1400 University Avenue, Madison, WI 53706, USA.
Summary
Genomic instability is not required for the initial development of colorectal adenomas. Studies using mouse models and human adenomas show stable chromosomes and microsatellites during early tumor formation, challenging existing hypotheses.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Loss of function of the adenomatous polyposis coli (APC) tumor suppressor gene is an early event in intestinal cancer.
- Genomic instability is hypothesized to drive tumor initiation by inducing APC loss in human colonic tumors.
Purpose of the Study:
- To analyze the earliest stages of intestinal tumorigenesis.
- To investigate the role of genomic instability in the initiation of colorectal adenomas.
Main Methods:
- Utilized a mouse model of inherited intestinal cancer (Apc(Min)/+).
- Analyzed karyotype and microsatellite stability in tumors from C57BL/6 Min/+ mice.
- Examined early, benign human colorectal adenomas.
Main Results:
- Tumors from C57BL/6 Min/+ mice exhibited stable karyotype and microsatellites.
- Homozygosity for the Apc Min allele in tumors can occur via homologous somatic recombination.
- No evidence of generalized chromosomal or microsatellite instability was found in early human colorectal adenomas.
Conclusions:
- Generalized chromosomal or microsatellite instability is not necessary for the initial development of colorectal adenomas.
- Findings challenge the hypothesis that genomic instability is a prerequisite for early colorectal adenoma formation.