Fostira Florentia, Papadimitriou Marios, Papadimitriou Christos
InRaSTES, Molecular Diagnostics Laboratory, National Centre for Scientific Research NCSR Demokritos, Athens, Greece.
Oncology Unit, Aretaieion University Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
Ann Transl Med. 2020 Dec;8(24):1703. doi: 10.21037/atm-20-1422.
Epithelial ovarian cancer (EOC) is probably the tumor type with the highest percentage of hereditary cases observed, irrespectively of selection criteria. A fourth to a fifth of unselected epithelial EOC patients carry pathogenic variants (PVs) in a number of genes, the majority of which encode for proteins involved in DNA repair pathways. and predisposing PVs were the first to be associated to ovarian cancer, with the advent in DNA sequencing technologies leading to the discovery and association of additional genes which compromise the homologous recombination (HR) pathway. In addition, PVs genes involved in mismatch repair (MMR) pathway, account for 10-15% of hereditary EOC. The identification of women with HR deficient ovarian cancers has significant clinical implications concerning chemotherapy regimen planning and development and use of targeted therapies as well. More specifically, in patients with PVs or HR deficiency maintenance treatment with poly(ADP-ribose) polymerase (PARP) inhibitors, either in the first line setting or in recurrent disease, improves the progression-free survival. But also patients with HR proficient tumors show a benefit. Therefore, genetic testing in ovarian cancer has a prognostic and predictive value. In this review, we discuss which ovarian cancer patients should be referred for genetic counseling and how to perform genetic testing. We also discuss the timing of genetic testing and its clinical relevance to status.
上皮性卵巢癌（EOC）可能是遗传性病例所占比例最高的肿瘤类型，无论选择标准如何。在未经过选择的上皮性EOC患者中，四分之一到五分之一携带多个基因的致病变异（PVs），其中大多数基因编码参与DNA修复途径的蛋白质。BRCA1和BRCA2基因的致病变异最早与卵巢癌相关，随着DNA测序技术的出现，又发现了其他一些影响同源重组（HR）途径的基因并将其与卵巢癌关联起来。此外，参与错配修复（MMR）途径的PVs基因占遗传性EOC的10%-15%。识别出患有HR缺陷型卵巢癌的女性对于化疗方案规划以及靶向治疗的开发和应用具有重要的临床意义。更具体地说，对于携带BRCA PVs或存在HR缺陷的患者，在一线治疗或复发性疾病中使用聚（ADP-核糖）聚合酶（PARP）抑制剂进行维持治疗可改善无进展生存期。但HR功能正常的肿瘤患者也能从中获益。因此，卵巢癌的基因检测具有预后和预测价值。在本综述中，我们讨论了哪些卵巢癌患者应转诊进行遗传咨询以及如何进行基因检测。我们还讨论了基因检测的时机及其与BRCA状态的临床相关性。
