Hutchcraft Megan L, Gallion Holly H, Kolesar Jill M
Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of Kentucky Markey Cancer Center, 800 Rose Street, Lexington, KY 40536-0263, USA.
Department of Pharmacy Practice & Science, University of Kentucky College of Pharmacy, 567 Todd Building, 789 South Limestone Street, Lexington, KY 40539-0596, USA.
Diagnostics (Basel). 2021 Jan 6;11(1):84. doi: 10.3390/diagnostics11010084.
Approximately 18% of ovarian cancers have an underlying genetic predisposition and many of the genetic alterations have become intervention and therapy targets. Although mutations in MutY homolog () are best known for associated polyposis and colorectal cancer, it plays a role in the development of ovarian cancer. In this review, we discuss the function of the gene, mutation epidemiology, and its mechanism for carcinogenesis. We additionally examine its emerging role in the development of ovarian cancer and how it may be used as a predictive and targetable biomarker. mutations may confer the risk of ovarian cancer by the failure of its well-known base excision repair mechanism or by failure to induce cell death. Biallelic germline mutations confer a 14% risk of ovarian cancer by age 70. A monoallelic germline mutation in conjunction with a somatic mutation may also contribute to the development of ovarian cancer. Resistance to platinum-based chemotherapeutic agents may be seen in tumors with monoallelic mutations, but platinum sensitivity in the biallelic setting. As is intimately associated with targetable molecular partners, therapeutic options for driven ovarian cancers include programed-death 1/programed-death ligand-1 inhibitors and poly-adenosine diphosphate ribose polymerase inhibitors. Understanding the function of and its associated partners is critical for determining screening, risk reduction, and therapeutic approaches for -driven ovarian cancers.
约18%的卵巢癌存在潜在的遗传易感性，许多基因改变已成为干预和治疗的靶点。尽管MutY同源物（）的突变因相关息肉病和结直肠癌而最为人所知，但它在卵巢癌的发生发展中也起作用。在本综述中，我们讨论了该基因的功能、突变流行病学及其致癌机制。我们还研究了它在卵巢癌发生发展中的新作用，以及它如何用作预测性和可靶向的生物标志物。突变可能因其著名的碱基切除修复机制失败或未能诱导细胞死亡而导致卵巢癌风险。双等位基因种系突变在70岁时导致卵巢癌的风险为14%。单等位基因种系突变与体细胞突变相结合也可能导致卵巢癌的发生。单等位基因突变的肿瘤可能对铂类化疗药物耐药，但双等位基因情况下对铂敏感。由于与可靶向的分子伴侣密切相关，由驱动的卵巢癌的治疗选择包括程序性死亡1/程序性死亡配体-1抑制剂和聚腺苷二磷酸核糖聚合酶抑制剂。了解及其相关伴侣的功能对于确定由驱动的卵巢癌的筛查、风险降低和治疗方法至关重要。
