ABSTRACT
Although Turner syndrome is most often sporadic, multigenerational recurrence has been reported more often in the offspring of women with mosaic or variant forms of Turner syndrome. We present a case in which natural conception in a woman with identified 45,X/46,XX mosaicism resulted in a fetus with a gain of a derivative X chromosome. The unexpected fetal finding prompted further cytogenetic evaluation of the patient and subsequent identification of an additional cell line with the same derivative X chromosome, not observed in the initial study. To our knowledge, this is the first case in which further investigation of an abnormal noninvasive prenatal screen resulted in the identification of both maternal and fetal sex chromosome abnormality. We discuss the discordant finding, similar cases, and potential phenotype with respect to skewed X inactivation. We also highlight the use of multiple testing methodologies to characterize the serendipitous identification of a derivative X chromosome.
ABSTRACT
Understanding the cell-of-origin of ovarian high grade serous cancer (HGSC) is the prerequisite for efficient prevention and early diagnosis of this most lethal gynecological cancer. Recently, a mesenchymal type of ovarian HGSC with the poorest prognosis among ovarian cancers was identified by both TCGA and AOCS studies. The cell-of-origin of this subtype of ovarian cancer is unknown. While pursuing studies to understand the role of the Hippo pathway in ovarian granulosa cell physiology and pathology, we unexpectedly found that the Yes-associated protein 1 (YAP1), the major effector of the Hippo signaling pathway, induced dedifferentiation and reprogramming of the ovarian granulosa cells, a unique type of ovarian follicular cells with mesenchymal lineage and high plasticity, leading to the development of high grade ovarian cancer with serous features. Our research results unveil a potential cell-of-origin for a subtype of HGSC with mesenchymal features.
