Genetic analysis of the human oncoprotein MDM2 in benign and malignant tumors of the salivary gland.
BACKGROUND
Genetic alterations of oncogene MDM2 promote malignant transformation of several human tumors. In tumors of the salivary gland, however, the genetic status of MDM2 has not been evaluated so far.


RESULTS
Benign and malignant tumors of the salivary gland (6 pleomorphic adenomas, 3 Warthin's tumors, 1 adenocarcinoma, 1 basal cell adenocarcinoma, 1 mucoepidermoid carcinoma, 3 acinic cell carcinomas, 2 adenoid cystic carcinoma, 1 squamous cell carcinoma) were analyzed by fluorescence-based PCR techniques and immunochemistry for MDM2 gene amplification, MDM2 gene expression, MDM2 gene mutation, MDM2 RNA splicing and MDM2 accumulation. Data show that all samples contained nonamplified MDM2 genes with nonmutant zinc finger regions. However, in two benign and two malignant samples, novel MDM2 mRNA splicing variant types 1 and 2 were detected. Furthermore, three malignant tumors revealed significant nuclear MDM2 accumulation. Correlation between levels of MDM2 mRNA and MDM2 protein could not be detected in the specimens.


CONCLUSIONS
The present study suggests that MDM2 gene mutation and gene amplification do not contribute to MDM2 accumulation detected in malignant tumors of the salivary gland. However, the role of novel MDM2 splicing variants in MDM2 expression and malignant transformation must be elucidated further.
Schlott
T
T
Department of Cytopathology, Georg August University, Göttingen, Germany. tschlott@med.uni-goettingen.de
Nagel
H
H
Laskawi
R
R
Eiffert
H
H
Droese
M
M
D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017398:Alternative Splicing; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D009687:Nuclear Proteins; D010307:Parotid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012470:Salivary Glands, Minor / Q000378:metabolism / Q000473:pathology
D004273:DNA, Neoplasm; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2