Mutations in the carcinoembryonic antigen gene in colorectal cancer patients: Implications on liver metastasis

Carcinoembryonic antigen (CEA) expression is used clinically to monitor pat ients with colorectal and other cancers. A subset of patients have extraord inarily high CEA levels that cannot be attributed solely to tumor load, We have shown mutations in the region of CEA (PELPK motif) responsible for its hepatic clearance in three of eight patients with high CEA levels, We used denaturing high-performance liquid chromatography to pro,ide evidence of p olymorphism in these patients. These mutations were scored by DNA cycle seq uencing and shown to be heterozygous. Tile patients with mutations in the P ELPK motif showed remarkably reduced circulatory clearance rates in an anim al model. A patient without mutation in the region showed normal clearance rates. Mutations in PELPK may affect structural stability and binding affin ity to the Kupffer cell receptor in the liver. These studies have implicati ons for the role of CEA as a facilitator of hepatic metastasis.