Putative parathyroid tumor suppressor on 1p: Independent molecular mechanisms of tumorigenesis from 11q allelic loss

Multiple endocrine neoplasia type 1 (MEN1) gene was identified to be a tumo r suppressor that encodes menin, playing an Important role in the developme nt of MEN1-associated tumors. Somatic MEN1 gene mutations also were detecte d in sporadic non-MEN1 endocrine tumors. Frequent loss of chromosomal arm l p has been reported in parathyroid adenomas, suggesting the existence of pu tative tumor-suppressor genes on 1p. In this study, we performed allelotypi ng of chromosomes 1p and 11q on 60 sporadic parathyroid adenomas. Thirteen of 48 (27%) informative tumors had allelic loss on 1p, and 18 of 50 (36%) h ad allelic loss on 11q. Ten of 18 tumors with 11q allelic loss successfully completed the sequence of the MEN1 gene coding region and splice junctions , and 3 of 10 (30%) tumors had no somatic mutation, indicating that other p utative tumor-suppressor genes on 11q may contribute to their tumorigenesis . Frequency of allelic losses on 1p was significantly higher in tumors with out 11q allelic losses (7 of 11 informative tumors [64%]) than in tumors wi th 11q allelic losses (3 of 17 informative tumors [18%]) by chi-square test (P = 0.0131; chi-square = 6.152). These observations suggested that putati ve tumor-suppressor genes locate on 1p, and pathways of their tumorigenesis are independent from inactivation of tumor-suppressor genes on 11q. (C) 20 01 by the National Kidney Foundation, Inc.