Critical Gene Mutated in Ovarian Cancer

FOXL2 gene mutated in nearly all adult-type granulosa-cell tumors

WEDNESDAY, June 10 (HealthDay News) -- A mutation in a gene known to be critical for the development of granulosa cells is found in nearly all adult-type granulosa-cell tumors (GCTs), a type of ovarian cancer, but not related tumor types, according to a study published online June 10 in New England Journal of Medicine.

Sohrab P. Shah, Ph.D., from the Centre for Translational and Applied Genomics in Vancouver, Canada, and colleagues performed whole-transcriptome sequencing of four GCTs to identify specific mutations that were not present in epithelial ovarian tumors, published human genomes, and databases of single nucleotide polymorphisms.

The researchers found that all four GCTs had a missense point mutation in the FOXL2 gene, which is known to be critical for granulosa-cell development. The mutation was present in 97 percent of adult-type GCTs, 21 percent of thecomas, and 10 percent of juvenile-type GCTs, but was absent from other types of malignant ovarian sex cord-stromal tumors and unrelated ovarian and breast tumors.

"Whole-transcriptome sequencing of four GCTs identified a single, recurrent somatic mutation (402C→G) in FOXL2 that was present in almost all morphologically identified adult-type GCTs," Shah and colleagues conclude. "Mutant FOXL2 is a potential driver in the pathogenesis of adult-type GCTs."

Two authors reported financial relationships with several pharmaceutical companies, and one author is listed as an inventor on a patent application on the use of the FOXL2 mutation in diagnosis and treatment.

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