Monoclonality and abnormal parathyroid hormone genes in parathyroid adenomas.
Previous work based on the relative tissue content of glucose-6-phosphate dehydrogenase isoenzymes suggested that parathyroid adenomas, like primary hyperplasia, may be multicellular (not clonal) in origin. We have reexamined this issue by using two independent molecular genetic methods. We report tumor-cell-specific restriction-fragment-length alterations involving the parathyroid hormone gene from two human parathyroid adenomas. These abnormal restriction fragments indicate that in each case a clonal proliferation of cells was present and also suggest that DNA alterations involving the parathyroid hormone locus may be important in the tumorigenesis or clonal evolution of some parathyroid adenomas. In addition, we used a restriction-fragment-length polymorphism in an X-linked gene (hypoxanthine phosphoribosyltransferase) to examine the clonality of eight parathyroid adenomas in women. Of these eight adenomas, six had the DNA hybridization pattern of monoclonality, and two had an equivocal pattern. None of five hyperplastic parathyroid glands had a monoclonal pattern. We conclude that some (and perhaps many) single parathyroid adenomas are monoclonal neoplasms. Our observations suggest that there is a fundamental biologic difference between parathyroid adenomas and primary hyperplasia--a difference that could prove useful in distinguishing these entities clinically.
Arnold
A
A
Endocrine Unit, Massachusetts General Hospital, Boston 02114.
Staunton
C E
CE
Kim
H G
HG
Gaz
R D
RD
Kronenberg
H M
HM
D000236:Adenoma / Q000235:genetics / Q000473:pathology*; D000328:Adult; D000368:Aged; D004247:DNA / Q000032:analysis; D004303:Dosage Compensation, Genetic; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D006965:Hyperplasia; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D010280:Parathyroid Glands / Q000473:pathology; D010281:Parathyroid Hormone / Q000235:genetics*; D010282:Parathyroid Neoplasms / Q000235:genetics / Q000473:pathology*; D014960:X Chromosome
D010281:Parathyroid Hormone; D004247:DNA; D007041:Hypoxanthine Phosphoribosyltransferase