MDM2 gene amplification is correlated to tumor progression but not to the presence of SNP309 or TP53 mutational status in primary colorectal cancers.
Mdm2 is the main regulator of p53 and is amplified in approximately 7% of all human cancers. MDM2 gene amplification as well as expression has been correlated to an increased tumorigenic potential. We have analyzed the prevalence of MDM2 gene amplifications and SNP309 in 284 colorectal tumors using a relatively new highly sensitive PCR/ligase detection reaction method in relation to TP53 mutational status and genomic instability. We found MDM2 to be amplified in 9% of the 284 colorectal cancers analyzed and a significantly higher proportion of tumors with high MDM2 gene amplification retained a wild-type p53 gene (P = 0.058). MDM2 gene amplification was significantly correlated to advanced tumor stage. Several small-molecule MDM2 antagonists have already been identified that either physically inhibit the p53-MDM2 binding or the E3 ligase function of MDM2. Our results suggest that MDM2 is a promising target for this type of cancer therapy in a substantial subgroup of colorectal cancers.
Forslund
Ann
A
Memorial Sloan-Kettering Cancer Center, Department of Surgery, Colorectal Surgery Service, New York, NY 10021, USA.
Zeng
Zhaoshi
Z
Qin
Li-Xuan
LX
Rosenberg
Shoshana
S
Ndubuisi
MacKevin
M
Pincas
Hanna
H
Gerald
William
W
Notterman
Daniel A
DA
Barany
Francis
F
Paty
Philip B
PB
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012015:Reference Standards; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2