Lynch H T, Casey M J, Lynch J, White T E, Godwin A K
Department of Preventive Medicine, Creighton University School of Medicine, Omaha, NE, USA.
Semin Oncol. 1998 Jun;25(3):265-80.
Ovarian cancer is a disease that will affect approximately 1% of American women during their lifetime, and contributes to more than 14,000 deaths annually. If not detected early, this disease has a 5-year survival rate of less than 20%. Ovarian cancer develops predominantly from the malignant transformation of a single cell type, the surface epithelium. Although the biological mechanisms of transformation remain unclear, it is probably a multistep process requiring an accumulation of genetic lesions in a number of different gene classes. Several proto-oncogenes, such as AKT2 and Ki-RAS, are activated during ovarian cancer development, with putative oncogene-containing chromosomal regions showing imbalances and DNA amplifications. A number of chromosomal regions are also lost in ovarian tumors, indicating that the inactivation of tumor suppressor genes, such as TP53, may also contribute to cancer development. An important recent advancement in the field of ovarian cancer research is the identification of the breast/ovarian cancer susceptibility genes, BRCA1 and BRCA2. Mutations in these two tumor suppressor genes are responsible for the majority of heritable forms of epithelial ovarian cancers. A second class of genes involved in DNA mismatch repair (MMR) are responsible for most cases of hereditary nonpolyposis colorectal cancer (HNPCC). HNPCC or Lynch II cancer syndrome patients are also at an increased risk for developing ovarian cancer. Individuals in cancer-prone kindreds are currently being screened for germline mutations in BRCA1, BRCA2, and several MMR genes (eg, MSH2, MLH1), and mutant allele carriers counseled for cancer risks. Issues related to counseling and management of women at high risk for developing ovarian cancer are discussed. Although BRCA1, BRCA2, and a number of MMR genes have been identified, many more genes involved in gynecologic malignancies remain to be discovered and the clinical significance of the cancer genes already known is still in its infancy.
卵巢癌是一种在一生中会影响约1%美国女性的疾病，每年导致超过14000人死亡。如果不及早发现，这种疾病的5年生存率低于20%。卵巢癌主要由单一细胞类型即表面上皮的恶性转化发展而来。尽管转化的生物学机制尚不清楚，但它可能是一个多步骤过程，需要在许多不同基因类别中积累遗传损伤。一些原癌基因，如AKT2和Ki-RAS，在卵巢癌发展过程中被激活，含有假定癌基因的染色体区域出现失衡和DNA扩增。在卵巢肿瘤中也有一些染色体区域缺失，这表明肿瘤抑制基因（如TP53）的失活也可能促进癌症发展。卵巢癌研究领域最近的一项重要进展是发现了乳腺癌/卵巢癌易感基因BRCA1和BRCA2。这两个肿瘤抑制基因的突变是大多数遗传性上皮性卵巢癌的病因。另一类参与DNA错配修复（MMR）的基因是大多数遗传性非息肉病性结直肠癌（HNPCC）的病因。HNPCC或林奇II型癌症综合征患者患卵巢癌的风险也增加。目前正在对癌症高发家族中的个体进行BRCA1、BRCA2和一些MMR基因（如MSH2、MLH1）的种系突变筛查，并为突变等位基因携带者提供癌症风险咨询。本文讨论了与卵巢癌高危女性咨询和管理相关的问题。尽管已经发现了BRCA1、BRCA2和一些MMR基因，但仍有许多参与妇科恶性肿瘤的基因有待发现，而且已知癌症基因的临床意义仍处于起步阶段。
