2016年6月2日讯/生物谷BIOON/--近日，研究揭示了表观遗传水平的早期变化对新的卵巢癌预防有重要作用。
根据发表在科学杂志《自然》上的文章显示，女性输卵管细胞BRCA基因突变的早期改变可能对卵巢癌预防提供了新方法，这样也减少了外科手术的必要性。
伦敦大学教授Martin Widschwendter研究分析了为什么携带BRCA1/2突变的女性会患卵巢癌。
Widschwendter和他的研究团队检测了115名女性术后生殖输卵管组织恢复情况，其中有56 人携带BRCA1/2突变，对照组的59人不携带BRCA1/2突变。他们分析了细胞的表观遗传特性。重要的是他们比较了同一个女性输卵管的两端的情况。
研究人员发现携带BRCA1或BRCA2基因突变的约60%女性的输卵管细胞菌毛的亚细胞活性根本性地发生了改变(顺便说一句，携带BRCA1突变体的女性比例会预期发展成为卵巢癌)。未携带BRCA突变体的女性的则没有什么改变。此外，研究人员发现一种酶(激活诱导胞嘧啶脱氨酶，AID)，该酶似乎会触发这个重编过程。
Widschwendter教授表示：“这些新发现让我们更进一步的了解了携带BRCA基因突变体的患者卵巢癌是如何发展的，这为预防卵巢癌提供了新方法。目前至关重要的最有效的预防方法是大幅降低手术的风险，这种手术会剥夺女性的荷尔蒙和绝经前生育能力。接下来的一步是研究影响基因重排药物的优点和寻找这类药物的生物标记。”
Athena Lamnisos说：“在他们开始之前阻止女性患癌症是我们研究项目的终极目标。要做到这一点，我们需要跟踪癌症早期的发展状况并理解它是如何开始的。它为患卵巢癌的妇女提供了希望，未来可能不需要进行外科手术就可以帮助预防卵巢癌。”（生物谷Bioon.com）
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Research points to possible new prevention strategies for ovarian cancer
Research revealing early changes at epigenetic level points to possible new prevention strategies for ovarian cancer The discovery of early changes in the cells of the Fallopian tubes of women carrying the BRCA genetic mutation could open the way for new preventative strategies for ovarian cancer, reducing the need for invasive surgery, according to research published today in science journal Nature Communications.
The research, undertaken by the Department of Women's Cancer at UCL led by Professor Martin Widschwendter and funded by The Eve Appeal, sought to understand why women with the BRCA1/2 mutations develop ovarian cancers and what happens in the cells where the cancers originate to trigger them. Widschwendter and his team examined the post-surgical reproductive tubal tissue from 115 women, 56 with the BRCA1/2 mutation and a control group of 59 without. They analysed the cells' epigenetic programmes, the 'software' which dictates how the cells read instructions encoded within the DNA. Crucially, they compared both ends of the Fallopian tubes (the fimbrial, closest to the ovary, and the uterine, closest to the womb), from the same woman.
The researchers discovered radically-altered subcellular activity occurring in the fimbrial tubal cells in approximately 60% of women carrying the BRCA1 or BRCA2 gene mutation (incidentally, the proportion of women with a BRCA1 mutation expected to develop ovarian cancer). These subcellular changes were similar to those seen in cells from ovarian cancer specimens. The changes were not seen in the women without BRCA mutations. In addition, the researchers identified an enzyme (activation-induced cytosine deaminase, AID) that appears to trigger this re-programming. Professor Widschwendter and his team are now further investigating their findings including examining whether they could benefit women who do not have a pre-disposing genetic mutation by facilitating the development of a non-invasive test which could potentially predict the occurrence of these cellular events in the tubal cells.
Professor Martin Widschwendter, Head of Department of Women's Cancer at University College London said: "These new findings take us a step closer to understanding how ovarian cancers develop in BRCA 1/2 gene mutation carriers, opening up new opportunities for ovarian cancer prevention. This is vital as at present the most effective method of prevention is drastic risk-reducing surgery which deprives women of their hormones and their ability to give birth prior to the menopause. The next steps will be to investigate the merit of drugs that affect epigenetic reprogramming and to look for biomarkers which allow safe monitoring of the effect of such drugs."
Athena Lamnisos, Chief Executive of The Eve Appeal said: "Stopping women's cancers before they start is the ultimate ambition of our research programme. To do this we need to track cancer development right back to its earliest development and understand how it begins. This research is an important step in achieving this ambition. It provides hope for women of the future who might not need to undergo such drastic, invasive surgery to aid the prevention of ovarian cancer.
