Am J Pathol  1999 Jun;154(6):1643-7 

Activating c-kit gene mutations in human germ cell tumors.

Tian Q, Frierson HF Jr, Krystal GW, Moskaluk CA.

Departments of Pathology, University of Virginia Health Sciences Center,
Charlottesville, USA.

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.

PMID: 10362788 [PubMed - indexed for MEDLINE]