PMID- 10362788
OWN - NLM
STAT- MEDLINE
DCOM- 19990714
LR  - 20181113
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 154
IP  - 6
DP  - 1999 Jun
TI  - Activating c-kit gene mutations in human germ cell tumors.
PG  - 1643-7
AB  - The c-kit gene encodes a tyrosine kinase receptor (KIT) that is required in
      normal spermatogenesis and is expressed in seminomas and dysgerminomas, a subset 
      of human germ cell tumors (GCTs). To determine whether activating mutations of
      the c-kit gene occur in GCTs, primary tissue samples of 33 testicular and ovarian
      tumors were examined for mutations in the juxtamembrane and phosphotransferase
      domains by polymerase chain reaction amplification and DNA sequencing. A novel
      missense mutation (D816H) was found in the phosphotransferase domain in tumors of
      seminoma/dysgerminoma differentiation. The c-kit alleles in nonneoplastic tissues
      from these patients were wild type, suggesting that the mutant alleles were
      acquired and selected for during malignant transformation. In cell transfection
      experiments, the D816H mutant protein was a constitutively activated kinase and
      was constitutively phosphorylated on tyrosine residues. This is the first
      description of an activating c-kit mutation in GCTs and is evidence that the KIT 
      signal transduction pathway is important in the pathogenesis of neoplasms with
      seminoma differentiation.
FAU - Tian, Q
AU  - Tian Q
AD  - Departments of Pathology, University of Virginia Health Sciences Center,
      Charlottesville, USA.
FAU - Frierson, H F Jr
AU  - Frierson HF Jr
FAU - Krystal, G W
AU  - Krystal GW
FAU - Moskaluk, C A
AU  - Moskaluk CA
LA  - eng
GR  - 5K08CA74431-02/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
SB  - IM
MH  - Amino Acid Substitution
MH  - Animals
MH  - COS Cells
MH  - DNA Mutational Analysis
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Neoplasms, Germ Cell and Embryonal/*enzymology/genetics
MH  - Phosphorylation
MH  - Point Mutation
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Proto-Oncogene Proteins c-kit/*genetics/metabolism
MH  - Transfection
MH  - Tyrosine/metabolism
PMC - PMC1876773
EDAT- 1999/06/11 10:00
MHDA- 2001/03/28 10:01
CRDT- 1999/06/11 10:00
PHST- 1999/06/11 10:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1999/06/11 10:00 [entrez]
AID - S0002-9440(10)65419-3 [pii]
AID - 10.1016/S0002-9440(10)65419-3 [doi]
PST - ppublish
SO  - Am J Pathol. 1999 Jun;154(6):1643-7. doi: 10.1016/S0002-9440(10)65419-3.