Maksimenko J, Irmejs A, Trofimovičs G, Bērziņa D, Skuja E, Purkalne G, Miklaševičs E, Gardovskis J
Institute of Oncology, Riga Stradins University, Dzirciema iela 16, Riga, LV1007 Latvia.
Hered Cancer Clin Pract. 2018 Jun 5;16:12. doi: 10.1186/s13053-018-0094-0. eCollection 2018.
Pathogenic founder mutations (c.4035delA, c.5266dupC) contribute to 3.77% of all consecutive primary breast cancers and 9.9% of all consecutive primary ovarian cancers. Identifying germline pathogenic gene variants in patients with primary breast and ovarian cancer could significantly impact the medical management of patients. The aim of the study was to evaluate the rate of pathogenic mutations in the 26 breast and ovarian cancer susceptibility genes in patients who meet the criteria for testing and to compare the accuracy of different selection criteria for second-line testing in a founder population.
Fifteen female probands and 1 male proband that met National Comprehensive Cancer Network (NCCN) criteria for testing were included in the study and underwent 26-gene panel testing. Fourteen probands had breast cancer, one proband had ovarian cancer, and one proband had both breast and ovarian cancer. In a 26-gene panel, the following breast and/or ovarian cancer susceptibility genes were included: and . All patients previously tested negative for founder mutations.
In 44% (7 out of 16) of tested probands, pathogenic mutations were identified. Six probands carried pathogenic mutations in , and one proband carried pathogenic mutations in . In patients, a variant of uncertain significance was found in , and . The Manchester scoring system showed a high accuracy (87.5%), high sensitivity (85.7%) and high specificity (88.9%) for the prediction of pathogenic non-founder mutations.
A relatively was The Manchester scoring system predicted the probability of non-founder pathogenic mutations with high accuracy.
致病性始祖突变（c.4035delA，c.5266dupC）在所有连续的原发性乳腺癌中占3.77%，在所有连续的原发性卵巢癌中占9.9%。识别原发性乳腺癌和卵巢癌患者的胚系致病性基因变异可能会对患者的医疗管理产生重大影响。本研究的目的是评估符合检测标准的患者中26个乳腺癌和卵巢癌易感基因的致病性突变率，并比较在始祖人群中二线检测不同选择标准的准确性。
15名女性先证者和1名男性先证者符合美国国立综合癌症网络（NCCN）检测标准，纳入本研究并接受26基因检测。14名先证者患有乳腺癌，1名先证者患有卵巢癌，1名先证者同时患有乳腺癌和卵巢癌。在一个26基因检测中，纳入了以下乳腺癌和/或卵巢癌易感基因： 和 。所有患者之前检测始祖突变均为阴性。
在44%（16例中的7例）检测的先证者中，鉴定出致病性突变。6名先证者在 中携带致病性突变，1名先证者在 中携带致病性突变。在患者中，在 、 和 中发现了意义未明的变异。曼彻斯特评分系统对致病性非始祖突变的预测具有较高的准确性（87.5%）、高敏感性（85.7%）和高特异性（88.9%）。
相对 是 曼彻斯特评分系统能高精度预测非始祖致病性突变的概率。
