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DNA from 61 unrelated patients with adenomatous polyposis coli (APC) was examined for mutations in three genes (DP1, SRP19, and DP2.5) located within a 100 kb region deleted in two of the patients. The intron-exon boundary sequences were defined for each of these genes, and single-strand conformation polymorphism analysis of exons from DP2.5 identified four(More)
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(More)
Small (100-260 kb), nested deletions were characterized in DNA from two unrelated patients with familial adenomatous polyposis coli (APC). Three candidate genes located within the deleted region were ascertained and a previous candidate gene, MCC, was shown to be located outside the deleted region. One of the new genes contained sequence identical to SRP19,(More)
An attenuated form of familial adenomatous polyposis coli, AAPC, causes relatively few colonic polyps, but still carries a significant risk of colon cancer. The mutant alleles responsible for this attenuated phenotype have been mapped in several families to the adenomatous polyposis coli (APC) locus on human chromosome 5q. Four distinct mutations in the APC(More)
Previous studies have shown that intestinal tumors from Apc(Min)(/+) (Min) mice and familial adenomatous polyposis (FAP) patients are often polyclonal. We sought to determine whether polyclonality is unique to tumors arising from hereditary predispositions or, instead, is a common feature of intestinal tumorigenesis in other pathways to tumorigenesis.(More)
Reverse transcription-PCR combined with either (a) restriction enzyme digestion and repeat PCR or (b) ligase chain reaction has identified two new alternatively spliced transcripts of the adenomatous polyposis coli (APC) gene. In one of these transcripts exons 1-4 and the first 16 bases of exon 5 are deleted; in the other exons 2-4 and the first 16 bases of(More)
The random collision hypothesis is a mathematical idealization of intestinal tumor formation that can account for the polyclonal origin of tumors without requiring a mechanistic description of clonal interaction. Using data from recent polyclonality studies in mice, we develop a statistical procedure to test the random collision hypothesis. Elements from(More)
Intestinal tumors from mice and humans can have a polyclonal origin. Statistical analyses indicate that the best explanation for this source of intratumoral heterogeneity is the presence of interactions among multiple progenitors. We sought to better understand the nature of these interactions. An initial progenitor could recruit others by facilitating the(More)
Stem cells share many properties with malignant cells, such as the ability to self-renew and proliferate. Cancer is believed to be a disease of stem cells. The gastrointestinal tract has high cancer prevalence partly because of rapid epithelial cell turnover and exposure to dietary toxins. The molecular pathways of carcinogenesis differ according to the(More)
The gene-trap lacZ reporter insertion, ROSA11, in the Cbx5 mouse gene illuminates the regulatory complexity of this locus in Apc(Min) (/+) mice. The insertion site of the β-Geo gene-trap element lies in the 24-kb intron proximal to the coding region of Cbx5. Transcript analysis indicates that two promoters for Cbx5 flank this insertion site. Heterozygotes(More)