Ovarian cancer (OC) represents the most dismal gynecological cancer. Pathobiology is poorly understood, mainly due to lack of appropriate study models. Organoids, defined as self-developing three-dimensional in vitro reconstructions of tissues, provide powerful tools to model human diseases. Here, we established organoid cultures from patient-derived OC, in particular from the most prevalent high-grade serous OC (HGSOC). Testing multiple culture medium components identified neuregulin-1 (NRG1) as key factor in maximizing OC organoid development and growth, although overall derivation efficiency remained moderate (36% for HGSOC patients, 44% for all patients together). Established organoid lines showed patient tumor-dependent morphology and disease characteristics, and recapitulated the parent tumor's marker expression and mutational landscape. Moreover, the organoids displayed tumor-specific sensitivity to clinical HGSOC chemotherapeutic drugs. Patient-derived OC organoids provide powerful tools for the study of the cancer's pathobiology (such as importance of the NRG1/ERBB pathway) as well as advanced preclinical tools for (personalized) drug screening and discovery.

When no suspects are identified in a forensic case as the donor of a biological trace, familial searching through the Y-chromosome can be used as an identification method to find paternally related males of the perpetrator. When a close Y-haplotype match is identified, the time to their most recent common ancestor (tMRCA) can be estimated to reconstruct their genealogy. To date, three online tMRCA calculators (McDonald, Walker and McGee) exist based on the infinite alleles model (IAM), but were not yet validated. In this study, the calculators were investigated using our genetic-genealogy database containing 1,126 genealogical pairs with known tMRCA, in which 42 Y-STR markers were analyzed. We observed that the McGee calculator is very discordant with our dataset, while the others give quite similar results. Overall, the tMRCAs from our genealogical pairs are located within the 95% CI, but are slightly underestimated for pairs with a close Y-haplotype match, and overestimated when more Y-STR differences are present. Additionally, their large 95% CI are not appropriate for genealogy reconstruction for forensic purposes. To further improve tMRCA estimations, individual Y-STR mutation rates and allele calls should be included to take hidden Y-STR differences into account.