Department of Genetics and Genomic Sciences, Division of Gynecologic Oncology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Gynecol Oncol. 2010 Nov;119(2):376-83. doi: 10.1016/j.ygyno.2010.07.026. Epub 2010 Aug 24.
A central challenge facing gynecologic oncology is achieving personalized care in ovarian cancer treatment. The current ovarian cancer classification scheme distinguishes tumors based on histopathologic subtype, grade, and surgical stage. Recent molecular investigations have highlighted distinguishing genetic features of certain tumors within a given category, and given the rapid pace of technologic advancement combined with plummeting costs for complete genomic sequencing this classification will markedly improve. Clinical studies have begun to explore the influence of currently known distinctions on the natural history of the disease, most recently with particular attention to the BRCA1 status of tumors. Mutations in the BRCA1 gene have long been known to increase a woman's risk of developing ovarian cancer. As has been shown, BRCA1-associated ovarian cancers may be associated with characteristic differences in therapeutic response and overall survival, and further defining these subsets may become instrumental in clinical decision-making. Therefore, given the eightfold difference (5-40%) in reported frequency of BRCA1 inactivation by methylation in the pioneering studies in the field, a critical re-appraisal of the literature, techniques, samples used, and interpretations of BRCA1 inactivation is warranted along with a review of the more recent and comprehensive molecular studies.
妇科肿瘤学面临的一个核心挑战是在卵巢癌治疗中实现个性化护理。目前的卵巢癌分类方案根据组织病理学亚型、分级和手术分期来区分肿瘤。最近的分子研究强调了在给定类别内某些肿瘤的区别性遗传特征，并且考虑到技术进步的快速步伐以及全基因组测序成本的急剧下降，这种分类将显著改善。临床研究已经开始探索目前已知差异对疾病自然史的影响，最近特别关注肿瘤的 BRCA1 状态。BRCA1 基因的突变早已被证实会增加女性患卵巢癌的风险。正如已经表明的那样，BRCA1 相关的卵巢癌可能与治疗反应和总体生存率的特征性差异有关，进一步定义这些亚组可能对临床决策具有重要意义。因此，鉴于该领域的开创性研究中报道的 BRCA1 甲基化失活频率有 8 倍（5-40%）的差异，有必要对文献、技术、使用的样本和 BRCA1 失活的解释进行批判性重新评估，并对最近更全面的分子研究进行回顾。
