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The retinoblastoma gene in human pituitary tumors
V L Cryns1, J M Alexander, A Klibanski
1Endocrine Unit, Massachusetts General Hospital, Boston.
Abstract:
Functional inactivation of the retinoblastoma (RB) tumor suppressor gene is important in the pathogenesis of many human tumors. Recently, the frequent occurrence of pituitary tumors was reported in mice genetically engineered to have one defective RB allele, a genetic background analogous to that of patients with familial retinoblastoma. The molecular pathogenesis of human pituitary tumors is largely unknown, and the potential role of RB gene inactivation in these neoplasms has not been examined. Consequently, we studied 20 human pituitary tumors (12 clinically nonfunctioning tumors, 4 somatotroph adenomas, 2 prolactinomas, and 2 corticotroph adenomas) for tumor-specific allelic loss of the RB gene using a highly informative polymorphic locus within the gene. Control leukocyte DNA samples from 18 of these 20 patients were heterozygous at this locus, permitting genetic evaluation of their paired tumor specimens. In contrast to the pituitary tumors in the mouse model, none of these 18 human tumors exhibited RB allelic loss. These findings indicate that RB gene inactivation probably does not play an important role in the pathogenesis of common types of human pituitary tumors.
Insights
Retinoblastoma (RB) gene inactivation is key in many cancers. However, this study found no RB gene loss in common human pituitary tumors, suggesting it
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Retinoblastoma (RB) tumor suppressor gene inactivation is crucial in human cancer development.
- Pituitary tumors in mice with a defective RB allele suggest a potential role for RB in pituitary tumorigenesis.
- The molecular basis of human pituitary tumors, particularly the involvement of the RB gene, remains largely unexamined.
Purpose of the Study:
- To investigate the potential role of RB gene inactivation in the pathogenesis of common human pituitary tumors.
- To determine if RB gene allelic loss occurs in various types of human pituitary adenomas.
Main Methods:
- Analysis of 20 human pituitary tumors (including nonfunctioning adenomas, somatotroph adenomas, prolactinomas, and corticotroph adenomas) for tumor-specific allelic loss of the RB gene.
- Utilized a highly informative polymorphic locus within the RB gene for genetic evaluation.
- Compared tumor DNA with constitutional DNA from patient leukocytes (18 paired samples).
Main Results:
- All 18 analyzed human pituitary tumors showed no evidence of RB allelic loss.
- This finding contrasts with observations in a mouse model of pituitary tumorigenesis linked to RB gene defects.
Conclusions:
- RB gene inactivation does not appear to be a significant factor in the development of common human pituitary tumors.
- The molecular pathogenesis of human pituitary tumors likely involves pathways independent of RB gene inactivation.