The specificity of the FOXL2 c.402C>G somatic mutation: a survey of solid tumors

PLoS One. 2009 Nov 24;4(11):e7988. doi: 10.1371/journal.pone.0007988.


Background: A somatic mutation in the FOXL2 gene is reported to be present in almost all (97%; 86/89) morphologically defined, adult-type, granulosa-cell tumors (A-GCTs). This FOXL2 c.402C>G mutation changes a highly conserved cysteine residue to a tryptophan (p.C134W). It was also found in a minority of other ovarian malignant stromal tumors, but not in benign ovarian stromal tumors or unrelated ovarian tumors or breast cancers.

Methodology/principal findings: Herein we studied other cancers and cell lines for the presence of this mutation. We screened DNA from 752 tumors of epithelial and mesenchymal origin and 28 ovarian cancer cell lines and 52 other cancer cell lines of varied origin. We found the FOXL2 c.402C>G mutation in an unreported A-GCT case and the A-GCT-derived cell line KGN. All other tumors and cell lines analyzed were mutation negative.

Conclusions/significance: In addition to proving that the KGN cell line is a useful model to study A-GCTs, these data show that the c.402C>G mutation in FOXL2 is not commonly found in a wide variety of other cancers and therefore it is likely pathognomonic for A-GCTs and closely related tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Cell Line, Tumor
  • Cysteine / genetics
  • Cytogenetics
  • Female
  • Forkhead Box Protein L2
  • Forkhead Transcription Factors / genetics*
  • Forkhead Transcription Factors / metabolism*
  • Genomics
  • Granulosa Cell Tumor / genetics*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Karyotyping
  • Mutation*
  • Ovarian Neoplasms / genetics
  • Tissue Distribution
  • Tryptophan / genetics


  • FOXL2 protein, human
  • Forkhead Box Protein L2
  • Forkhead Transcription Factors
  • Tryptophan
  • Cysteine