Human pituitary adenomas show no loss of heterozygosity at the retinoblastoma gene locus.
The retinoblastoma tumor suppressor gene (RB1) is inactivated in hereditary and sporadic forms of retinoblastoma as well as in a number of other sporadic tumors. The majority of human pituitary tumors have been shown to be monoclonal neoplasms, suggesting that 1 or more somatic mutations are involved in the clonal expansion of a single progenitor cell. Recently, a high percentage of transgenic mice containing a disrupted RB1 allele have been shown to develop pituitary tumors. To investigate whether RB1 inactivation contributes to the development of human pituitary adenomas, we searched for loss of heterozygosity (LOH) within the RB1 gene locus in a variety of human pituitary adenomas. We screened 34 adenomas for LOH using a polymerase chain reaction (PCR)-based microsatellite polymorphic marker at the RB1 gene locus. In addition, a variable number of tandem repeat markers from within the RB1 gene was also used to search for LOH in 14 tumors. We found no LOH or microsatellite instability at the RB1 locus in any of the informative cases (30 of 34). Additionally, we showed that 4 representative adenomas from female patients are monoclonal in origin using a PCR-based clonality analysis assay. We conclude that the RB1 gene shows no LOH in a variety of human pituitary adenomas and that PCR-based microsatellite markers can serve as a useful tool for LOH analysis in human pituitary tumors.
Zhu
J
J
Neurosurgical Laboratories, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Leon
S P
SP
Beggs
A H
AH
Busque
L
L
Gilliland
D G
DG
Black
P M
PM
D000236:Adenoma / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016161:Genes, Retinoblastoma; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010911:Pituitary Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
D004273:DNA, Neoplasm