PMID- 17243166
OWN - NLM
STAT- MEDLINE
DCOM- 20070418
LR  - 20120604
IS  - 1045-2257 (Print)
IS  - 1045-2257 (Linking)
VI  - 46
IP  - 4
DP  - 2007 Apr
TI  - Mutation and expression analyses of the MET and CDKN2A genes in rhabdomyosarcoma 
      with emphasis on MET overexpression.
PG  - 348-58
AB  - Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood. The 
      simultaneous loss of Ink4a/Arf function and disruption of Met signaling in 
      Ink4a/Arf-/- mice transgenic for hepatocyte growth factor/scatter factor (HGF/SF) 
      induces RMS with extremely high penetrance and short latency. To address the 
      roles of MET and CDKN2A (p16INK4A/p14ARF) in human RMS, we performed mutational 
      analyses in 39 samples of RMS by PCR-SSCP. No mutations were detected in exons 
      14-21 of MET whereas a nonsense mutation at codon 80 of p16(INK4A) was identified 
      in an alveolar RMS cell line. We also quantified the relative expression levels 
      and DNA copy numbers of these genes in seven cell lines and 17 fresh tumors by 
      real-time quantitative PCR. Expression of MET was detected in all samples; 
      however, more than 10-fold difference was found in the samples with higher or 
      lower expression level, despite a normal DNA copy number. The protein expression 
      level was consistent with that of mRNA, and in cell lines with a higher 
      expression level, MET was constitutively activated. Notably, the expression level 
      of MET was significantly higher in patients who died (P = 0.02), in patients with 
      stage IV (P = 0.04), as well as in patients with PAX3-FKHR chimeric transcript (P 
      = 0.04). On the other hand, reduced or absent expression of p16INK4A and/or 
      p14(ARF) showed no significant correlation with the clinicopathological 
      parameters, except for the age at diagnosis. Our data suggest that MET plays a 
      role in the progression of RMS.
CI  - (c) 2007 Wiley-Liss, Inc.
FAU - Chen, Yuyan
AU  - Chen Y
AD  - Department of Pediatrics, Graduate School of Medicine, University of Tokyo, 
      Tokyo, Japan.
FAU - Takita, Junko
AU  - Takita J
FAU - Mizuguchi, Masashi
AU  - Mizuguchi M
FAU - Tanaka, Kiyoshi
AU  - Tanaka K
FAU - Ida, Kohmei
AU  - Ida K
FAU - Koh, Katsuyoshi
AU  - Koh K
FAU - Igarashi, Takashi
AU  - Igarashi T
FAU - Hanada, Ryoji
AU  - Hanada R
FAU - Tanaka, Yukichi
AU  - Tanaka Y
FAU - Park, Myoung-Ja
AU  - Park MJ
FAU - Hayashi, Yasuhide
AU  - Hayashi Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Genes Chromosomes Cancer
JT  - Genes, chromosomes & cancer
JID - 9007329
RN  - 0 (Codon, Nonsense)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Growth Factor)
RN  - EC 2.7.10.1 (MET protein, human)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Age of Onset
MH  - Cell Line, Tumor
MH  - Codon, Nonsense
MH  - Cyclin-Dependent Kinase Inhibitor p16/*genetics
MH  - *DNA Mutational Analysis
MH  - *Gene Expression Profiling
MH  - Humans
MH  - Mutation, Missense
MH  - Point Mutation
MH  - Proto-Oncogene Proteins/biosynthesis/*genetics
MH  - Proto-Oncogene Proteins c-met
MH  - Receptors, Growth Factor/biosynthesis/*genetics
MH  - Rhabdomyosarcoma/*genetics/metabolism
EDAT- 2007/01/24 09:00
MHDA- 2007/04/19 09:00
CRDT- 2007/01/24 09:00
PHST- 2007/01/24 09:00 [pubmed]
PHST- 2007/04/19 09:00 [medline]
PHST- 2007/01/24 09:00 [entrez]
AID - 10.1002/gcc.20416 [doi]
PST - ppublish
SO  - Genes Chromosomes Cancer. 2007 Apr;46(4):348-58. doi: 10.1002/gcc.20416.