PMID- 10327054
OWN - NLM
STAT- MEDLINE
DCOM- 19990603
LR  - 20220208
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 14
DP  - 1999 Apr 8
TI  - Novel mutations of the MET proto-oncogene in papillary renal carcinomas.
PG  - 2343-50
AB  - Hereditary papillary renal carcinoma (HPRC) is characterized by multiple,
      bilateral papillary renal carcinomas. Previously, we demonstrated missense
      mutations in the tyrosine kinase domain of the MET proto-oncogene in HPRC and a
      subset of sporadic papillary renal carcinomas. In this study, we screened a large
      panel of sporadic papillary renal carcinomas and various solid tumors for
      mutations in the MET proto-oncogene. Summarizing these and previous results,
      mutations of the MET proto-oncogene were detected in 17/129 sporadic papillary
      renal carcinomas but not in other solid tumors. We detected five novel missense
      mutations; three of five mutations were located in the ATP-binding region of the 
      tyrosine kinase domain of MET. One novel mutation in MET, V1110I, was located at 
      a codon homologous to an activating mutation in the c-erbB proto-oncogene. These 
      mutations caused constitutive phosphorylation of MET when transfected into NIH3T3
      cells. Molecular modeling studies suggest that these activating mutations
      interfere with the intrasteric mechanism of tyrosine kinase autoinhibition and
      facilitate transition to the active form of the MET kinase. The low frequency of 
      MET mutations in noninherited papillary renal carcinomas (PRC) suggests that
      noninherited PRC may develop by a different mechanism than hereditary papillary
      renal carcinoma.
FAU - Schmidt, L
AU  - Schmidt L
AD  - Intramural Research Support Program, SAIC Frederick, National Cancer
      Institute-Frederick Cancer Research and Development Center, Maryland 21702, USA.
FAU - Junker, K
AU  - Junker K
FAU - Nakaigawa, N
AU  - Nakaigawa N
FAU - Kinjerski, T
AU  - Kinjerski T
FAU - Weirich, G
AU  - Weirich G
FAU - Miller, M
AU  - Miller M
FAU - Lubensky, I
AU  - Lubensky I
FAU - Neumann, H P
AU  - Neumann HP
FAU - Brauch, H
AU  - Brauch H
FAU - Decker, J
AU  - Decker J
FAU - Vocke, C
AU  - Vocke C
FAU - Brown, J A
AU  - Brown JA
FAU - Jenkins, R
AU  - Jenkins R
FAU - Richard, S
AU  - Richard S
FAU - Bergerheim, U
AU  - Bergerheim U
FAU - Gerrard, B
AU  - Gerrard B
FAU - Dean, M
AU  - Dean M
FAU - Linehan, W M
AU  - Linehan WM
FAU - Zbar, B
AU  - Zbar B
LA  - eng
SI  - PDB/1IRK
GR  - N01-CO-56000/CO/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Codon)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (MAS1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Mas)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - 3T3 Cells/metabolism
MH  - Adenoma/genetics/metabolism
MH  - Adenosine Triphosphate/metabolism
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - Carcinoma, Papillary/*genetics
MH  - Cell Transformation, Neoplastic/genetics
MH  - Codon/genetics
MH  - DNA Mutational Analysis
MH  - DNA, Neoplasm/*genetics
MH  - Humans
MH  - Kidney Neoplasms/*genetics
MH  - Mice
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Neoplasm Proteins/chemistry/*genetics/metabolism
MH  - Neoplastic Syndromes, Hereditary/genetics
MH  - Phosphorylation
MH  - *Point Mutation
MH  - Protein Conformation
MH  - Protein Processing, Post-Translational/genetics
MH  - Proto-Oncogene Mas
MH  - Proto-Oncogene Proteins c-met/chemistry/*genetics/metabolism
MH  - *Proto-Oncogenes
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - Transfection
EDAT- 1999/05/18 00:00
MHDA- 1999/05/18 00:01
CRDT- 1999/05/18 00:00
PHST- 1999/05/18 00:00 [pubmed]
PHST- 1999/05/18 00:01 [medline]
PHST- 1999/05/18 00:00 [entrez]
AID - 10.1038/sj.onc.1202547 [doi]
PST - ppublish
SO  - Oncogene. 1999 Apr 8;18(14):2343-50. doi: 10.1038/sj.onc.1202547.