Oncotarget | FOXL2 homozygous genotype and chromosome instability are associated with recurrence in adult granulosa cell tumors of the ovary

Oncotarget Volume 11, Issue 4: The present study focused on the influence of the FOXL2 genotype and copy number variations in recurrence by comparing the primary tumor with recurrent lesions in the same patient.

The authors also observed that three recurrent tumors and one primary tumor appeared to be homozygous for the FOXL2 c.402C>G mutation.

Despite the small number of matching primary and recurrent tumors analyzed here, the present study is the first to have shown that the FOXL2 homozygous genotype and CIN are prevalent in recurrent aGCTs.

Dr. Stéphanie Trudel from EA4666, LNPC, Université de Picardie Jules Verne in Amiens, France as well as the Laboratoire d'Oncobiologie moléculaire, Centre Hospitalier Universitaire Amiens-Picardie in Amiens, France said in their Oncotarget article, "Granulosa cell tumors (GCTs) of the ovary are very rare, and account for less than 5% of all ovarian malignancies."

Figure 1: The qPCR allelic discrimination assay. Green dots represent samples that were heterozygous for the FOXL2 c.402C>G mutation (with a fluorescent signal from both wild-type and mutant probes), blue dots represent samples that were homozygous for the FOXL2 c.402C>G mutation (with a fluorescent signal from the mutant probe only), red dots represent wild-type samples (with a fluorescent signal from the wild-type probe only), black dots represent samples for which the genotype could not be determined, and yellow dots are the no-template controls. Each sample was tested in duplicate. Ctrl-: negative control; NTCs: no-template controls.

The primary molecular feature of aGCTs is the presence of a single pathognomonic missense mutation in the FOXL2 gene; this mutation is found in 94% to 97% of aGCTs, and is mainly observed in the heterozygous state.

Adult GCTs are commonly associated with slow, indolent disease progression, a high recurrence rate, and aggressive recurrence.

The pervasive somatic FOXL2 mutation is likely to have a crucial role in the pathogenesis of aGCTs, and the mutations function in this setting has been extensively explored.

Given that a heterozygous FOXL2 c.402 C>G mutation is present in almost all aGCTs, it is likely that other genetic changes are involved in the oncogenesis of aGCT. Molecular markers that could predict recurrence and/or aggressive disease would be a great asset in the management of aGCT.

The Trudel Research Team concluded in their Oncotarget paper that it is not yet known which of these processes are involved in aGCT, although recent genetic studies of primary and recurrent tumors have identified mutations in the promoter of the TERT gene, in the KMT2D gene and in the TP53 gene.

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Full text - https://doi.org/10.18632/oncotarget.27447

Correspondence to - Stéphanie Trudel - trudel.s@chu-toulouse.fr

Keywords - granulosa cell tumor, recurrence, FOXL2, array comparative genomic hybridization, chromosome instability