MDM2 gene amplification is correlated to tumor progression but not to the presence of SNP309 or TP53 mutational status in primary colorectal cancers Journal Article

  

Authors:	Forslund, A.; Zeng, Z.; Qin, L. X.; Rosenberg, S.; Ndubuisi, M.; Pincas, H.; Gerald, W.; Notterman, D. A.; Barany, F.; Paty, P. B.
Article Title:	MDM2 gene amplification is correlated to tumor progression but not to the presence of SNP309 or TP53 mutational status in primary colorectal cancers
Abstract:	Mdm2 is the main regulator of p53 and is amplified in ∼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. Copyright © 2008 American Association for Cancer Research.
Keywords:	adult; controlled study; aged; aged, 80 and over; middle aged; gene mutation; human cell; single nucleotide polymorphism; mutation; polymorphism, single nucleotide; cancer staging; genetic analysis; polymerase chain reaction; protein function; colorectal cancer; in situ hybridization, fluorescence; disease association; gene amplification; gene expression; prevalence; protein binding; genotype; mutational analysis; wild type; protein p53; colorectal neoplasms; gene expression regulation, neoplastic; statistical significance; reference standards; genomic instability; disease progression; tumor suppressor protein p53; dna mutational analysis; tumor growth; ubiquitin protein ligase e3; protein mdm2; proto-oncogene proteins c-mdm2
Journal Title:	Molecular Cancer Research
Volume:	6
Issue:	2
ISSN:	1541-7786
Publisher:	American Association for Cancer Research
Date Published:	2008-02-01
Start Page:	205
End Page:	211
Language:	English
DOI:	10.1158/1541-7786.mcr-07-0239
PUBMED:	18314481
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-40349098614&partnerID=40&md5=f1de71b11ebfbbca6302d5ebb46dbba9
Notes:	--- - "Cited By (since 1996): 5" - "Export Date: 17 November 2011" - "CODEN: MCROC" - "Source: Scopus"

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