mdm-2 oncogene expression in non-Hodgkin's lymphomas.
The mdm-2 protein is a 90-kD protein that forms a complex with the p53 protein, enabling cells from some human neoplasms to overcome the growth-suppressing activity of p53. Most non-Hodgkin's lymphomas lack p53 mutations, and the mechanism of inactivation of tumor suppressive function remains obscure. To assess the role of mdm-2 in lymphomagenesis, 22 cases were evaluated for mdm-2 gene amplification or rearrangement in Southern blots. Localization of the mdm-2 protein was performed on cryostat sections and compared with expression of the p53 gene product. No case exhibited mdm-2 gene amplification or rearrangement, but overexpression of nuclear mdm-2 gene protein product was found in three of six diffuse large cell (B-cell immunoblastic) lymphomas (30-70% of the tumor cells stained). The mdm-2 protein was absent from low- and intermediate-grade lymphomas with the exception of a few cells (5% or less) in four cases. The mdm-2-positive cases stained negative for p53. Southern blot analysis showed that samples overexpressing mdm-2 did not have amplification or rearrangement of the gene. In summary, amplification of the mdm-2 gene does not appear to play a prominent role in the pathogenesis of non-Hodgkin's lymphomas, although overexpression of the protein gene product occurs, particularly in high-grade neoplasms.
Kawamata
N
N
Department of Medical Oncology, Cedars Sinai Medical Center, Los Angeles, California, USA.
Miller
C
C
Levy
V
V
Shintaku
I P
IP
Koeffler
H P
HP
Said
J W
JW
D015139:Blotting, Southern; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000473:pathology*; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D011519:Proto-Oncogenes; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2