Characterization of a TP53 Somatic Variant of Unknown Function From an Ovarian Cancer Patient Using Organoid Culture and Computational Modeling
In our proof-of-concept study of 1 patient with stage IIIC carcinosarcoma of the ovary, we discovered a rare mutation in the tumor suppressor, TP53, that results in the deletion of N131. Immunofluorescence imaging of the organoid culture revealed hyperstaining of p53 protein. Computational modeling suggests this residue is important for maintaining protein conformation. Drug screening identified the combination of a proteasome inhibitor with a histone deacetylase inhibitor as the most effective treatment. These data provide evidence for the successful culture of a patient tumor and analysis of drug response ex vivo.
Abstract OBJECTIVE: To investigate racial disparities in uterine carcinosarcoma (UCS) and ovarian carcinosarcoma (OCS) in Commission on Cancer®-accredited facilities. METHODS: Non-Hispanic Black (NHB) and non-Hispanic White (NHW) women in the National Cancer Database diagnosed with stage I-IV UCS or OCS between 2004 and 2014 were eligible. Differences by disease site or race were compared using Chi-square test and multivariate Cox analysis. RESULTS: There were 2830 NHBs and 7366 NHWs with UCS, and 280 NHBs and 2586 NHWs with OCS. Diagnosis of UCS was more common in NHBs (11.5%) vs. NHWs (3.7%) and in...
CONCLUSIONS: Our data show that MSI is present in a substantial proportion of endometrioid ovarian cancers but can also occur in other tumor subtypes. MMR deficiency/MSI typically involves the entire tumor mass, suggesting that MMR inactivation occurs early in tumorigenesis in a subset of ovarian cancers. PMID: 31924330 [PubMed - as supplied by publisher]
ConclusionHerein, we describe distinct DNA methylation signatures in uterine neoplasms and show that array-based DNA methylation analysis holds promise as an ancillary tool to further characterize uterine neoplasms, especially in cases which are diagnostically challenging by conventional techniques.
CONCLUSION: Herein, we describe distinct DNA methylation signatures in uterine neoplasms and show that array-based DNA methylation analysis holds promise as an ancillary tool to further characterize uterine neoplasms, especially in cases which are diagnostically challenging by conventional techniques. PMID: 31768620 [PubMed - as supplied by publisher]
GATA binding protein 3 (GATA3) immunohistochemistry is primarily used as a marker of breast and urothelial differentiation, particularly in metastatic settings. In the gynecologic tract it also serves a robust marker for mesonephric and trophoblastic tumors. However, expression has also been described in more common malignancies of gynecologic tract including ovarian, endometrial, and cervical carcinomas. Data on the distribution of GATA3 expression in gynecologic malignancies is somewhat limited, particularly across different histologic subtypes of ovarian, endometrial, and cervical carcinomas. To assess the rates of GATA...
Conditions: Fallopian Tube Carcinosarcoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Fallopian Tube Undifferentiated Carcinoma; Germline BRCA1 Gene Mutation; Germline BRCA2 Gene Mutation; High Grade Fallopian Tube Serous A denocarcinoma; High Grade Ovarian Serous Adenocarcinoma; Ovarian Clear Cell Tumor; Ovarian Seromucinous Carcinoma; Ovaria...
ConclusionsUnlike ovarian cancer, less than half of the patients undergoing NACT for endometrial cancer underwent IDS, none had a complete response, and 41% had disease progression during NACT. However, endometrial cancer patients who underwent IDS had a high rate of optimal cytoreduction. Both response to NACT and IDS were associated with improved survival.
Conditions: Ovarian Cancer; Carcinosarcoma Intervention: Drug: Pamiparib Sponsor: Australia New Zealand Gynaecological Oncology Group Not yet recruiting