Schultz Kris Ann P, Harris Anne K, Finch Michael, Dehner Louis P, Brown Jubilee B, Gershenson David M, Young Robert H, Field Amanda, Yu Weiying, Turner Joyce, Cost Nicholas G, Schneider Dominik T, Stewart Douglas R, Frazier A Lindsay, Messinger Yoav, Hill D Ashley
International Ovarian and Testicular Stromal Tumor Registry, Children's Minnesota, Minneapolis, MN, United States; Cancer and Blood Disorders, Children's Minnesota, Minneapolis, MN, United States.
International Ovarian and Testicular Stromal Tumor Registry, Children's Minnesota, Minneapolis, MN, United States; Cancer and Blood Disorders, Children's Minnesota, Minneapolis, MN, United States.
Gynecol Oncol. 2017 Dec;147(3):521-527. doi: 10.1016/j.ygyno.2017.09.034. Epub 2017 Oct 14.
Ovarian sex cord-stromal tumors (OSCST) include juvenile granulosa cell tumors (JGCT), Sertoli-Leydig cell tumor (SLCT) and gynandroblastoma (GAB) among others. These ovarian sex cord-stromal tumors as well as other tumors including pleuropulmonary blastoma (PPB) may be associated with DICER1 mutations. We sought to describe the clinical and genetic findings from the first 107 individuals enrolled in the International Ovarian and Testicular Stromal Tumor Registry.
Medical and family history were obtained for individuals consecutively enrolled in the International Ovarian and Testicular Stromal Tumor Registry. Pathology was centrally reviewed. DICER1 sequencing was performed on blood and tumor tissue.
Of the 107 participants, 49 had SLCT, 25 had JGCT and 5 had GAB. Nearly all (36/37) SLCTs and 4/4 GAB tested had a DICER1 mutation in an RNase IIIb domain hotspot; approximately half of these individuals had a predisposing germline DICER1 mutation. Metachronous SLCTs were seen in 3 individuals with germline DICER1 mutations. Other DICER1-associated conditions were seen in 19% of patients with SLCT or GAB. Three children of women with SLCT were diagnosed with PPB based on genetic testing and clinical screening during the course of this study. All were diagnosed with PPB in its earliest and most curable form (Type I), were treated with surgery alone, and are alive without evidence of disease.
Recognition of the distinct genetic basis for a group of these tumors improves precise classification in difficult cases and promotes mutation-based screening and early detection.
卵巢性索间质肿瘤（OSCST）包括幼年型颗粒细胞瘤（JGCT）、支持-间质细胞瘤（SLCT）和两性母细胞瘤（GAB）等。这些卵巢性索间质肿瘤以及其他肿瘤，包括胸膜肺母细胞瘤（PPB），可能与DICER1突变有关。我们试图描述国际卵巢和睾丸间质肿瘤登记处登记的首批107名患者的临床和基因研究结果。
收集连续登记在国际卵巢和睾丸间质肿瘤登记处的患者的医学和家族史。对病理进行集中复审。对血液和肿瘤组织进行DICER1测序。
107名参与者中，49例为SLCT，25例为JGCT，5例为GAB。几乎所有检测的SLCT（36/37）和GAB（4/4）在核糖核酸酶IIIb结构域热点区域都有DICER1突变；这些个体中约一半有易患性种系DICER1突变。3名种系DICER1突变的个体出现了异时性SLCT。19%的SLCT或GAB患者出现了其他与DICER1相关的病症。在本研究过程中，3名SLCT患者的子女经基因检测和临床筛查被诊断为PPB。所有患者均被诊断为最早且最可治愈的PPB（I型），仅接受了手术治疗，目前存活且无疾病迹象。
认识到这类肿瘤的独特遗传基础有助于在疑难病例中进行精确分类，并促进基于突变的筛查和早期检测。
