Loss of wild-type MEN1 gene expression in multiple endocrine neoplasia type 1-associated parathyroid adenoma

Multiple endocrine neoplasia type 1 (MEN1) is a human hereditary tumor synd rome characterized by the development of endocrine adenomas of the parathyr oid, anterior pituitary, and enteropancreatic tissue. Several lines of evid ence have implicated the recently identified MEN1 gene located on chromosom e 11q13 as a recessive tumor suppressor gene. Here, we analyzed MEN1 wild-t ype gene expression in tumors from a large MEN1 kindred. A deletion of codo ns 227-228 (678del6) located in exon 4 was found in tumor and peripheral bl ood complementary DNA using a simplified single-strand conformational polym orphism (SSCP) approach well suited for clinical MEN1 mutation screening. T he identified 678del6 cDNA mutation deletes a potential phosphorylation sit e (Tyr227) and corresponds to a germ line mutation co-segregating with dise ase phenotype in this MEN1 family. Loss of heterozygosity analysis by fluor escent microsatellite PCR showed an exclusive loss of the MEN1 wild-type (a nd retention of the mutated) allele detectable in DNA from microdissected p arathyroid and pancreatic, but not in adrenal, adenomas. Our findings confi rm the synergism between MEN1 gene mutations and subsequent MEN1 allelic lo sses in the tumorigenesis of MEN1-associated adenomas.