| Autor: |
Roze JF; Department of Gynaecological Oncology, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands., Kutzera J; Department of Genetics, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands., Koole W; Department of Genetics, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands., Ausems MGEM; Department of Genetics, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands., Engelstad K; FM Ambulance, Fargo, ND 58078, USA., Piek JMJ; Department of Obstetrics and Gynaecology, Catharina Hospital, 5623 EJ Eindhoven, The Netherlands., de Kroon CD; Department of Obstetrics and Gynaecology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., Verheijen RHM; Department of Gynaecological Oncology, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands., van Haaften G; Department of Genetics, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands., Zweemer RP; Department of Gynaecological Oncology, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands., Monroe GR; Department of Gynaecological Oncology, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands. |
| Abstrakt: |
Adult granulosa cell tumor (AGCT) is a rare ovarian cancer subtype, with a peak incidence around 50-55 years. Although AGCT can occur in specific syndromes, a genetic predisposition for AGCT has not been identified. The aim of this study is to identify a genetic variant in families with AGCT patients, potentially contributing to tumor evolution. We identified four families, each including two women diagnosed with AGCT. Whole-genome sequencing was performed to identify overlapping germline variants or affected genes. Familial relationship was evaluated using genealogy and genomic analyses. Patient characteristics, medical (family) history, and pedigrees were collected. Findings were compared to a reference group of 33 unrelated AGCT patients. Mean age at diagnosis was 38 years (range from 17 to 60) versus 51 years in the reference group, and seven of eight patients were premenopausal. In two families, three first degree relatives were diagnosed with breast cancer. Furthermore, polycystic ovary syndrome (PCOS) and subfertility was reported in three families. Predicted deleterious variants in PIK3C2G, BMP5, and LRP2 were identified. In conclusion, AGCTs occur in families and could potentially be hereditary. In these families, the age of AGCT diagnosis is lower and cases of breast cancer, PCOS, and subfertility are present. We could not identify an overlapping genetic variant or affected locus that may explain a genetic predisposition for AGCT. |
