Somatic genetic events linked to the Apc locus in intestinal adenomas of the Min mouse.
We have found previously that all spontaneous intestinal adenomas from Apc+/ApcMin mice lose the wild type Apc marker on two genetic backgrounds. On the (AKR x B6)F1 background, this event involves loss of the entire homolog of mouse chromosome 18 carrying Apc+. This chromosome carries both the Mcc and Dcc genes, which are homologs of genes that have been implicated in human colorectal cancer. To determine whether the loss of alleles of Mcc and/or Dcc is necessary for the formation of intestinal adenomas, subchromosomal somatic events were induced by gamma-irradiation. The observed spectrum of intrachromosomal somatic genetic losses rules out a requirement for loss of heterozygosity at either locus during adenoma formation. Subchromosomal allelic losses linked to Apc+ occur spontaneously on other genetic backgrounds. In the majority of these events, the Apc+ allele itself was somatically lost, as judged by the wild type marker at the Min site. However, on the [M. musculus castaneous (CAST) x B6-Min]F1 and (129/Sv x B6-Min)F1 backgrounds, spontaneous adenomas were observed in which the wild type marker at the Min site was retained. Further analysis will be required to determine whether these exceptions involve intra-Apc mutations. If not, then these events would illustrate routes to intestinal neoplasia that do not require complete inactivation of wild type Apc function.
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McArdle Laboratory for Cancer Research and Laboratory of Genetics, University of Wisconsin Medical School, Madison 53706, USA.
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D000236:Adenoma / Q000235:genetics*; D000483:Alleles; D000818:Animals; D004195:Disease Models, Animal; D005819:Genetic Markers; D007414:Intestinal Neoplasms / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL
D005819:Genetic Markers