GENOMIC LOCALIZATION OF NOVEL CANDIDATE TUMOR-SUPPRESSOR GENE LOCI INHUMAN PARATHYROID ADENOMAS

Only one oncogene, cyclin D1/PRAD1, has an established role in parathy roid tumorigenesis, and parathyroid tumor suppressor genes on chromoso me arms 1p and 11q, which still have not been identified, have also be en implicated by loss of heterozygosity analysis, To investigate wheth er other putative tumor suppressor genes are involved in the pathogene sis of parathyroid adenomas, we performed a more comprehensive analysi s of allelic losses in these tumors. Using 39 polymorphic markers, we examined each chromosome arm, excluding the short arms of the acrocent ric chromosomes, In 25 parathyroid adenomas, frequent loss of heterozy gosity, in >25% of the informative cases, was observed on chromosome a rms 6q (30%), 11p (27%), and 15q (35%), in addition to previously repo rted 1p (30%) and 11q (38%) allelic losses, To more specifically local ize the smallest shared regions of molecular genetic deletion, we exam ined the following chromosomes in greater detail: chromosome 6 (9 addi tional markers), chromosome 11 (8 additional markers), and chromosome 15 (15 additional markers), The regions most commonly deleted in these tumors were 6q22-23, 6q26-27, 11q13, 15q11-21, and 15q26-qter. All tu mors with 11p loss had patterns consistent with monosomy for chromosom e 11, These findings provide novel evidence for the existence of tumor suppressor genes on chromosome arms 6q and 15q that contribute common ly to the pathogenesis of parathyroid adenomas.