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.
Imanishi
Y
Y
Center for Molecular Medicine, University of Connecticut Health Center, Farmington, CT, USA. imanishi@med.osaka-cu.ac.jp
Tahara
H
H
D000236:Adenoma / Q000150:complications / Q000235:genetics*; D019457:Chromosome Breakage; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D016368:Frameshift Mutation; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D006961:Hyperparathyroidism / Q000209:etiology; D009154:Mutation; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics*; D010282:Parathyroid Neoplasms / Q000150:complications / Q000235:genetics*; D011518:Proto-Oncogene Proteins
C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins