| Abstract: | ![]()
We have found previously that all spontaneous intestinal adenomas from Apc+/Apr mice lose the wild type Apc marker on two genetic backgrounds. On the (AKR X B6)F, background, this event involves loss of the entire homolog of mouse chromosome 18 carrying Apt+. This chromosome carries both the Mcc and Dcc genes, which are homologs of genh 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 γ-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 t o Apc+ occur spontaneously on other genetic backgrounds. In the majority of these events, the Apt+ allele itself was somatically lost, as judged by the wild type marker at the Min site. However, on the [M. musculus costoneus (CAST) X B6-Min]F, and (I 29/Sv X B6-Min)F, backgrounds, spontaneous adenomas were observed in which the wild type marker at the Min site was retained. Further analysis will be required t o 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. Genes Chromosom Cancer 17:194–198 (1996). |
