Absence of mutations in the functional domains of the human MDM2 oncogene in non-small cell lung carcinomas.
Increasing evidence suggests that MDM2 oncoprotein participates in a complex array of interactions with a plethora of molecules, including cell-cycle and transcriptional regulators, as well as determinants of the cell differentiation and senescence. The tumorigenic potential of MDM2 is mainly determined by overexpression due to gene amplification, mRNA overexpression and possibly translational enhancement. Although artificially created mutations have been demonstrated to abolish normal MDM2 function, there is little information concerning its mutational status in human tissues. In this study, we screened all the functional domains of MDM2 for mutations in a series of 58 non-small cell lung carcinomas (NSCLCs), but none was found. Therefore, we report that MDM2 mutations are an extremely rare phenomenon of non-small cell lung carcinogenesis. A putative explanation for this observation may be the labyrinth of interactions necessary for cell viability, in which MDM2 takes part, a finding also supported by its stringent interspecies conservation.
Mariatos
G
G
Laboratory of Histology and Embryology, Medical School, University of Athens, Athens, Greece.
Gorgoulis
V G
VG
Kotsinas
A
A
Zacharatos
P
P
Kokotas
S
S
Yannoukakos
D
D
Kittas
C
C
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005784:Gene Amplification; D015870:Gene Expression; D016158:Genes, p53; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2
D018076:DNA, Complementary; D004273:DNA, Neoplasm; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2