Department of Obstetrics & Gynaecology, University of Auckland, New Zealand.
School of Women's and Infants' Health, University of Western Australia, Australia.
Gynecol Oncol. 2014 May;133(2):382-7. doi: 10.1016/j.ygyno.2013.12.012. Epub 2013 Dec 14.
It has been four years since the discovery of the FOXL2 402C>G mutation in adult ovarian granulosa cell tumours. Yet to date, there have been few studies which have investigated the precise role of the mutation in tumour pathogenesis. This review aims to summarise the research in this area, proposes a mechanism of action for the mutation, and explores the implications for clinical practice and future therapeutics.
A literature search was performed with the keywords 'granulosa cell tumour' and 'FOXL2' on PubMed.
Although the search returned 52 articles, of these only nine publications investigate the pathogenic effect of the mutant FOXL2 allele. Mutant FOXL2 maintains some of the transcriptional activity of the wildtype allele, but there is a subtle alteration of the expression in a unique suite of cancer-related genes. The mutation appears to deregulate the anti-proliferative transforming growth factor beta (TGF-β) pathway and this may contribute to the pathogenesis of adult GCTs. The inability of mutant FOXL2 to elicit an effective apoptotic signalling cascade may also be important in GCT pathogenesis.
The 402C>G mutation in FOXL2 is central to the development of adult granulosa cell tumours. Based on the evidence, we suggest that FOXL2 is an oncogene or tumour suppressor depending on the genetic context that is the GCT subtype.
FOXL2 402C>G 突变在成人卵巢颗粒细胞瘤中的发现已经过去了四年。然而，迄今为止，很少有研究调查该突变在肿瘤发病机制中的确切作用。本综述旨在总结该领域的研究，提出该突变的作用机制，并探讨其对临床实践和未来治疗的意义。
在 PubMed 上使用关键词“granulosa cell tumour”和“FOXL2”进行文献检索。
尽管搜索返回了 52 篇文章，但其中只有 9 篇出版物研究了突变 FOXL2 等位基因的致病作用。突变 FOXL2 保持野生型等位基因的部分转录活性，但在独特的一套与癌症相关的基因中表达存在微妙改变。该突变似乎使抗增殖转化生长因子β（TGF-β）途径失活，这可能导致成人 GCT 的发病机制。突变 FOXL2 不能引发有效的细胞凋亡信号级联反应，这在 GCT 发病机制中也可能很重要。
FOXL2 中的 402C>G 突变是成人颗粒细胞瘤发生发展的关键。基于证据，我们建议 FOXL2 根据遗传背景（即 GCT 亚型）是癌基因或肿瘤抑制基因。
