These results support (i) that vitamin D, alone or in combination with calcium, may modify APC, β-catenin, and E-cadherin expression in humans in directions hypothesized to reduce risk for colorectal neoplasms; (ii) vitamin D as a potential chemopreventive agent against colorectal neoplasms; and (iii) the potential of APC, β-catenin, and E-cadherin expression as treatable, pre-neoplastic risk biomarkers for colorectal neoplasms.
The prevalence of APC truncation mutants in colorectal tumors and the ability of these alleles to act dominantly to inhibit the mitotic spindle place chromosome instability at the earliest stage of colorectal cancer progression (i.e., prior to deregulation of beta-catenin).
The APC gene has been found to be mutated during the development of sporadic colorectal tumors as well as in the germ line of familial adenomatous polyposis patients.
These findings suggest that a mutation of the APC gene may play an important role in the genesis of sporadic hepatoblastomas, and the mechanisms of APC gene alteration may be different from those reported previously for colorectal tumors.
When combined with previously published data, our results show that there is interdependence of the "two hits" at APC in sporadic colorectal tumors as well as in FAP.
Thus, we suggest that oncogenic K-ras represents a key player during an alternative, serrated pathway to colorectal cancer and hence propose RAS-RAF-MEK signaling apart from APC as an additional gatekeeper in colorectal tumor development.
High sensitivity scanning of colorectal tumors and matched plasma DNA for mutations in APC, TP53, K-RAS, and BRAF genes with a novel DHPLC fluorescence detection platform.