PMID- 20461754
OWN - NLM
STAT- MEDLINE
DCOM- 20100909
LR  - 20161125
IS  - 1098-2264 (Electronic)
IS  - 1045-2257 (Linking)
VI  - 49
IP  - 7
DP  - 2010 Jul
TI  - MDM2 gene amplification in colorectal cancer is associated with disease 
      progression at the primary site, but inversely correlated with distant 
      metastasis.
PG  - 620-9
LID - 10.1002/gcc.20774 [doi]
AB  - MDM2 is a crucial negative regulator of the TP53 tumor suppressor and almost 10% 
      of human tumors exhibit MDM2 amplification. Although TP53 pathway perturbation 
      has been extensively examined in colorectal cancer (CRC), only one previous 
      report has evaluated MDM2 amplification in relation to clinicopathological 
      factors. In that report, MDM2 amplification was shown to be associated with 
      disease progression from Dukes' Stages A to D. In this study, we investigated 
      MDM2 amplification by quantitative PCR and fluorescence in situ hybridization 
      (FISH) together with the SNP309 genotypes, and analyzed the correlations with 
      TP53 and KRAS mutations and clinicopathological features in 211 Japanese CRC 
      patients. MDM2 amplification was detected in 8% of the specimens and its 
      incidence was significantly higher in Dukes' stage C than in the combined earlier 
      Stages A and B (P = 0.025). Unexpectedly, the incidence was significantly 
      decreased in Stage D metastatic disease (P = 0.043). The copy number gain ranged 
      from four to eight copies and was generally concordant with gain of centromere 12 
      using FISH analysis. Together with the results of centromere 1 FISH and TP53 copy 
      number assessment, the MDM2 increment most likely resulted from chromosome 12 
      gain. The mechanism of the copy number gain and incidence in Dukes' Stage D 
      differed considerably from the previous report. Ethnic or geographic factors 
      could be responsible for these differences. Several promising therapeutic 
      strategies targeting the TP53-MDM2 system are being developed. Further 
      understanding of the significance of MDM2 and MDM2 amplification in CRC is 
      required to facilitate personalized treatment for CRC patients.
CI  - (c) 2010 Wiley-Liss, Inc.
FAU - Sugano, Nobuhiro
AU  - Sugano N
AD  - Department of Gastrointestinal Surgery, Kanagawa Cancer Center Hospital, 
      Yokohama, Japan.
FAU - Suda, Tetsuji
AU  - Suda T
FAU - Godai, Ten-I
AU  - Godai TI
FAU - Tsuchida, Kazuhito
AU  - Tsuchida K
FAU - Shiozawa, Manabu
AU  - Shiozawa M
FAU - Sekiguchi, Hironobu
AU  - Sekiguchi H
FAU - Yoshihara, Mitsuyo
AU  - Yoshihara M
FAU - Matsukuma, Shoichi
AU  - Matsukuma S
FAU - Sakuma, Yuji
AU  - Sakuma Y
FAU - Tsuchiya, Eiju
AU  - Tsuchiya E
FAU - Kameda, Yoichi
AU  - Kameda Y
FAU - Akaike, Makoto
AU  - Akaike M
FAU - Miyagi, Yohei
AU  - Miyagi Y
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Genes Chromosomes Cancer
JT  - Genes, chromosomes & cancer
JID - 9007329
RN  - EC 2.3.2.27 (MDM2 protein, human)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
SB  - IM
MH  - Colorectal Neoplasms/*genetics/*pathology
MH  - *Gene Amplification
MH  - Genes, ras
MH  - Genotype
MH  - Humans
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single Nucleotide
MH  - Proto-Oncogene Proteins c-mdm2
EDAT- 2010/05/13 06:00
MHDA- 2010/09/10 06:00
CRDT- 2010/05/13 06:00
PHST- 2010/05/13 06:00 [entrez]
PHST- 2010/05/13 06:00 [pubmed]
PHST- 2010/09/10 06:00 [medline]
AID - 10.1002/gcc.20774 [doi]
PST - ppublish
SO  - Genes Chromosomes Cancer. 2010 Jul;49(7):620-9. doi: 10.1002/gcc.20774.