TY - JOUR
T1 - DICER1-related Sertoli-Leydig cell tumor and gynandroblastoma
T2 - Clinical and genetic findings from the International Ovarian and Testicular Stromal Tumor Registry
AU - Schultz, Kris Ann P.
AU - Harris, Anne K.
AU - Finch, Michael
AU - Dehner, Louis P.
AU - Brown, Jubilee B.
AU - Gershenson, David M.
AU - Young, Robert H.
AU - Field, Amanda
AU - Yu, Weiying
AU - Turner, Joyce
AU - Cost, Nicholas G.
AU - Schneider, Dominik T.
AU - Stewart, Douglas R.
AU - Frazier, A. Lindsay
AU - Messinger, Yoav
AU - Hill, D. Ashley
N1 - Funding Information:
The authors each state that he/she has no conflicts of interest to disclose. This work is supported by National Institutes of Health grant NCI R01CA143167 and The Parson's Foundation (DAH,YM). The International Ovarian and Testicular Stromal Tumor Registry is supported by St. Baldrick’s Foundation, Pine Tree Apple Tennis Classic Foundation, Hyundai Hope on Wheels and the Randy Shaver Cancer Research and Community Fund. DTS is supported by the German Childhood Cancer Foundation. Supported in part by the Intramural Research Program of the Divisions of Cancer Epidemiology and Genetics, National Cancer Institute.
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/12
Y1 - 2017/12
N2 - Background 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. Methods 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. Results 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. Conclusions 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.
AB - Background 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. Methods 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. Results 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. Conclusions 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.
KW - DICER1
KW - Gynandroblastoma
KW - Ovary
KW - Sertoli-Leydig cell tumor
KW - Sex cord-stromal tumor
UR - http://www.scopus.com/inward/record.url?scp=85031330947&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2017.09.034
DO - 10.1016/j.ygyno.2017.09.034
M3 - Article
C2 - 29037807
AN - SCOPUS:85031330947
SN - 0090-8258
VL - 147
SP - 521
EP - 527
JO - Gynecologic oncology
JF - Gynecologic oncology
IS - 3
ER -