Promoter mutations are no major cause of PTTG overexpression in pituitary adenomas.
OBJECTIVE
The pituitary tumour transforming gene (PTTG) was proven to cause transformation of NIH3T3 fibroblasts, which produce tumours when transplanted into immunodeficient mice. PTTG is overexpressed in about 90% of pituitary adenomas. The reason for its overexpression is still unclear.


METHODS
Because promoter mutations may play a role for an altered regulation of PTTG transcription in the pituitary adenomas, we analysed two promoter regions which were characterized previously as functionally important.


METHODS
Twenty-five patients of both sexes with pituitary adenomas, mainly null-cell adenomas, were included in this study.


METHODS
Both DNA regions were amplified from paraffin sections by PCR and analysed for small deletions or insertions on polyacrylamide gels in all patients. In 16 cases both DNA regions were sequenced to detect base substitutions.


RESULTS
No deletions/insertions and no tumour-specific substitutions were found. In three homopolymeric regions a polymorphism was detected, which also occurred in control sequences. In addition, these tracts showed some degree of length instability.


CONCLUSIONS
Promoter mutations do not play a major role for the enhanced PTTG transcription in pituitary adenomas. Therefore, DNA-binding proteins, hypomethylation or other epigenetic factors may be responsible for PTTG overexpression.
Kanakis
D
D
Department of Neuropathology, University of Magdeburg, Magdeburg, Germany. dimitrios.kanakis@medizin.uni-magdeburg.de
Kirches
E
E
Mawrin
C
C
Dietzmann
K
K
D024506:5' Flanking Region / Q000235:genetics*; D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D010911:Pituitary Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic; D064249:Securin
D009363:Neoplasm Proteins; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human