The gene for multiple endocrine neoplasia type 1 (MENi), an inherited predisposition to neuroendocrine neoplasm of the parathyroid glands, the pancreatic islet parenchyma, and the anterior pituitary gland, was recently mapped to chromosome 11q13 based on genetic linkage in families. We now show that the pathogenesis of MEN1-associated parathyroid lesions involves unmaking of a recessive mutation at the disease locus and that sporadic primary hyperparathyroidism shares the same mechanisms. MENi patients and from 24 patients with sporadic primary hyperparathyroidism were fresh-frozen and stored at -700C.The parathyroid lesions 11-3 LU-HPT and HPT-EZ were obtained from members of the LU and EZ kindreds (3). Specimens of insulinoma parenchyma from case II-1 of the LU kindred (3) were also included.Pituitary tumors from 27 cases, all but one (APA-23) with no signs of MEN1, were obtained by a trans-sphenoidal surgical approach and treated in the same manner. Four

All human chromosomes were screened in 52 human breast carcinomas for the occurrence of allele losses, in order to identify genomic alterations involved in initiation and progression of the disease. Loss of chromosome 22 alleles was detected in 6 out of 8 lobular carcinomas, while chromosome 17 losses were most frequent in ductal carcinomas. Furthermore, patients who developed advanced disease after many years of mild clinical course showed significantly higher frequencies of allele losses in their primary tumors, compared to patients with a persistently mild disease course. Finally, in one case, molecular examination suggested a translocation t(10;17) with coamplification of the ERBB2 oncogene and chromosome 10 sequences present in the two tumors from this patient, consistent with one of the tumors being a metastasis originating from a subclone of cells in the other tumor.