FOXL2^C134W: much ado about something!^†

Recent studies have suggested that the unique FOXL2^C134W mutation, which is pathognomonic for adult granulosa cell tumours of the ovary, is a tumour suppressor gene. In a recent issue of The Journal of Pathology, a detailed study by Pilsworth et al seeks to rebut the proposition that the FOXL2^C134W mutation, which uniquely characterises adult granulosa cell tumours of the ovary, leads to reduced transcript levels with the implication that FOXL2 is a tumour suppressor gene. The study provides compelling evidence that both wild-type and mutant FOXL2 transcripts and protein are expressed at equivalent levels. In the context of other recent studies, one is drawn to the conclusion that FOXL2^C134W is a gain-of-function mutation whose impact is mediated through enhanced interactions with the SMAD transcription factor complex.