Related Experiment Videos
Ras mutations in human pituitary tumors
H J Karga1, J M Alexander, E T Hedley-Whyte
1Department of Medicine, Massachusetts General General Hospital, Boston 02114.
Abstract:
The cellular basis for pituitary neoplasia is poorly understood. Mutations that activate the ras protooncogenes have been identified in a number of different types of human cancers and potentially represent one of the genetic alterations that occur in pituitary tumors. In this study we examined 19 pituitary tumors for the occurrence of ras mutations. The tumor types included 11 nonfunctioning adenomas, 6 somatotroph adenomas, and 2 prolactinomas. Each of the three ras genes (K-ras, N-ras, and H-ras) was amplified from pituitary tumor DNA using the polymerase chain reaction. Oligonucleotide-specific hybridization was used to screen for mutations that inhibit GTPase activity and cause activation of the ras oncogene. No ras mutations were observed in 18 of the pituitary adenomas. However, a mutation was identified in codon 12 of the H-ras gene (Gly to Val) in a recurrent prolactinoma that was highly invasive and ultimately proved to be fatal. We conclude that ras mutations are uncommon in pituitary adenomas, but may provide a marker for highly invasive tumors.
Insights
Ras mutations are rare in pituitary tumors, but a specific H-ras gene mutation was found in a fatal, invasive prolactinoma. This finding suggests ras mutations may indicate aggressive pituitary neoplasia.
Area of Science:
- Oncology
- Genetics
- Endocrinology
Background:
- The cellular origins of pituitary tumors (neoplasia) are not well understood.
- Activating mutations in ras proto-oncogenes are implicated in various human cancers.
- Ras gene alterations are potential genetic factors in pituitary tumor development.
Purpose of the Study:
- To investigate the presence and significance of ras mutations in pituitary tumors.
- To determine if ras mutations are associated with specific pituitary tumor subtypes or invasiveness.
Main Methods:
- Analyzed DNA from 19 pituitary tumors (11 nonfunctioning adenomas, 6 somatotroph adenomas, 2 prolactinomas).
- Amplified K-ras, N-ras, and H-ras genes using polymerase chain reaction.
- Screened for mutations affecting GTPase activity via oligonucleotide-specific hybridization.
Main Results:
- No ras mutations were detected in 18 out of 19 pituitary adenomas.
- A mutation in codon 12 of the H-ras gene (Glycine to Valine) was identified in one recurrent prolactinoma.
- This specific prolactinoma was highly invasive and associated with a fatal outcome.
Conclusions:
- Ras mutations are infrequent genetic alterations in pituitary adenomas.
- The identified H-ras mutation in an aggressive prolactinoma may serve as a potential biomarker for highly invasive pituitary tumors.