IDENTICAL APC EXON-15 MUTATIONS RESULT IN A VARIABLE PHENOTYPE IN FAMILIAL ADENOMATOUS POLYPOSIS

Germ-line mutations in the adenomatous polyposis coli (APC) gene resul t in familial adenomatous polyposis coli (APC), an inherited syndrome that predisposes affected individuals to early onset of colorectal can cer. Somatic APC mutations also have been detected in sporadic colon t umors. We have used single strand conformational polymorphism (SSCP) a nalysis to scan a region of the APC gene that frequently is mutated in both APC and sporadic colorectal cancer. Four truncating mutations we re found between codons 1060 and 1327 in 17 of 68 unrelated APC indivi duals. Fourteen of these persons carried either of two previously desc ribed five-nucleotide deletions which represent about 20% of APC mutat ions in these pedigrees. Patients with mutations in this region of exo n 15 develop a classic APC colonic phenotype with multiple, diffuse ad enomas developing by the second or third decade. However, the density of adenomas and the extracolonic disease manifestations associated wit h this syndrome are variable among individuals with identical APC muta tions.