Identification of FAP Locus Genes from Chromosome 5q21

TLDR

Chromosome 5q21 harbors genes implicated in colorectal cancer, particularly familial adenomatous polyposis, and the MCC gene was previously identified through its mutation in human colorectal tumors. The study aimed to clone a region tightly linked to FAP to identify genes at this locus and to investigate the roles of MCC and APC and their potential interaction in colorectal neoplasia. Researchers cloned a portion of the FAP‑linked region, isolated six contiguous 5.5‑Mb contigs, and used subclones from these contigs to locate and position six genes expressed in normal colonic mucosa. APC and MCC were identified at this locus; both encode large proteins with coiled‑coil domains, are broadly expressed, and are likely contributors to colorectal tumorigenesis.

Abstract

Recent studies suggest that one or more genes on chromosome 5q21 are important for the development of colorectal cancers, particularly those associated with familial adenomatous polyposis (FAP). To facilitate the identification of genes from this locus, a portion of the region that is tightly linked to FAP was cloned. Six contiguous stretches of sequence (contigs) containing approximately 5.5 Mb of DNA were isolated. Subclones from these contigs were used to identify and position six genes, all of which were expressed in normal colonic mucosa. Two of these genes (APC and MCC) are likely to contribute to colorectal tumorigenesis. The MCC gene had previously been identified by virtue of its mutation in human colorectal tumors. The APC gene was identified in a contig initiated from the MCC gene and was found to encode an unusually large protein. These two closely spaced genes encode proteins predicted to contain coiled-coil regions. Both genes were also expressed in a wide variety of tissues. Further studies of MCC and APC and their potential interaction should prove useful for understanding colorectal neoplasia.