Clonality of parathyroid adenomas and normal parathyroid glands was an
alyzed by a method based on restriction fragment length polymorphism o
f the X-chromosome-linked phosphoglycerokinase (PGK) gene and on rando
m inactivation of the gene by methylation. Through the introduction of
the polymerase chain reaction to this method, clonal analysis could b
e performed on small DNA samples prepared from cryostat sections of th
ese specimens. Every normal parathyroid gland was found to be polyclon
al while every parathyroid adenoma was found to be monoclonal. When DN
A samples obtained from four widely separated sites of an adenoma were
independently analyzed, each sample was found to be monoclonal and, i
n addition, the same allele of PGK gene was inactivated. These results
suggest that parathyroid adenoma, which has a single cell origin, is
a true neoplasm and that its pathogenesis is probably different from t
hat of parathyroid hyperplasia which is polyclonal in origin.