LOCALIZATION OF THE MULTIPLE ENDOCRINE NEOPLASIA TYPE-I (MEN1) GENE BASED ON TUMOR LOSS OF HETEROZYGOSITY ANALYSIS

Multiple endocrine neoplasia type I (MEN1) is an inherited syndrome th at results in parathyroid, anterior pituitary, and pancreatic and duod enal endocrine tumors as well as foregut carcinoids in affected patien ts, The gene responsible for the disease has been linked to chromosome 11q13, We analyzed loss of heterozygosity (LOH) in 188 tumors from 81 patients in an attempt to further define the location of the MEN1 gen e, Both tumors from MEN1 patients and corresponding sporadic tumors we re analyzed, Tumor types included parathyroid, gastrinoma, pancreatic endocrine, pituitary, and lung carcinoid, Six tumors (three MEN1 and t hree sporadic tumors) were identified that provided important LOH boun daries, Four tumors (two parathyroid tumors, one gastrinoma, and one l ung carcinoid tumor) showed allelic loss that placed the MEN1 gene dis tal to marker PYGM. Two tumors (one gastrinoma and one parathyroid tum or) showed an LOH boundary that placed the gene proximal to D11S449, o ne of which further moved the telomeric boundary to D11S4936, Taken to gether, the present data suggest that the MEN1 gene lies between PYGM and D11S4936, a region of approximately 300 kb on chromosome 11q13.