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 tumor suppressor that encodes menin, playing an important role in the development of MEN1-associated tumors. Somatic MEN1 gene mutations also were detected in sporadic non-MEN1 endocrine tumors. Frequent loss of chromosomal arm 1p has been reported in parathyroid adenomas, suggesting the existence of putative tumor-suppressor genes on 1p. In this study, we performed allelotyping 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%) had 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 putative tumor-suppressor genes on 11q may contribute to their tumorigenesis. Frequency of allelic losses on 1p was significantly higher in tumors without 11q allelic losses (7 of 11 informative tumors [64%]) than in tumors with 11q allelic losses (3 of 17 informative tumors [18%]) by chi-square test (P = 0.0131; chi-square = 6.152). These observations suggested that putative tumor-suppressor genes locate on 1p, and pathways of their tumorigenesis are independent from inactivation of tumor-suppressor genes on 11q.