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.
Source: Clinical Obstetrics and Gynecology - Category: OBGYN Tags: New and Novel Treatments for Gynecologic Cancer Source Type: research

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kowska Human chorionic gonadotropin (hCG) is a well-known hormone produced by the trophoblast during pregnancy as well as by both trophoblastic and non-trophoblastic tumors. hCG is built from two subunits: α (hCGα) and β (hCGβ). The hormone-specific β subunit is encoded by six allelic genes: CGB3, CGB5, CGB6, CGB7, CGB8, and CGB9, mapped to the 19q13.32 locus. This gene cluster also encompasses the CGB1 and CGB2 genes, which were originally considered to be pseudogenes, but as documented by several studies are transcriptionally active. Even though the protein products of t...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Article Source Type: research
Background: Primary Epithelial Ovarian Cancer (EOC), a malignant gynecologic disease, is considered one of the leading causes of mortality in women. The development of Liver Metastases (LM) in women with primary ovarian cancer commonly results in a poorer prognosis. This retrospective population-based study aims to measure the prevalence, prognostic factors, and associated risk factors for epithelial ovarian cancer patients with liver metastases (EOCLM).Materials and Methods: The current study cohort of patients based on the Surveillance, Epidemiology, and End Results (SEER) database identified with primary ovarian cancer ...
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
We report the case of a 50-yr-old woman who was diagnosed with concomitant endometrial adenocarcinoma and uterine leiomyosarcoma. The sarcomatous neoplasm was positive for anti-smooth muscle actin and CD10, and focally positive for Cytokeratin AE1/AE3 and Cytokeratin Cam 5.2. She underwent total abdominal hysterectomy with bilateral salpingoopherectomy followed by radiation, brachytherapy, and chemotherapy. Three years later, she presented with cough and dyspnea and was found to have pulmonary metastasis. These tumor cells were positive for anti-smooth muscle actin, Cytokeratin AE1/AE3, Cytokeratin Cam 5.2, and epithelial ...
Source: International Journal of Gynecological Pathology - Category: Pathology Tags: PATHOLOGY OF THE CORPUS: CASE REPORTS Source Type: research
Conclusion: The outcome of gynecologic carcinosarcoma in the second-line setting is poor, especially in patients with a short treatment-free interval.Oncology
Source: Oncology - Category: Cancer & Oncology Source Type: research
CONCLUSION: The outcome of gynecologic carcinosarcoma in the second-line setting is poor, especially in patients with a short treatment-free interval. PMID: 32526764 [PubMed - as supplied by publisher]
Source: Oncology - Category: Cancer & Oncology Authors: Tags: Oncology Source Type: research
Abstract Gynaecologic and breast cancers share some similarities at the molecular level. The aims of our study are to highlight the similarities and differences about IDO1, an important immune-related gene in female cancers. The NGS data from TCGA of cervical squamous cell carcinoma (CESC), ovarian serous cystadenocarcinoma (OV), uterine corpus endometrial carcinoma (UCEC), uterine carcinosarcoma (UCS) and breast invasive carcinoma (BRCA) were analysed to identify molecular features, and clinically significant and potential therapeutic targets of IDO1. We found IDO1 was significantly up-regulated in four gynaecolo...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
In this study, we assessed the immunohistochemical expression of c-KIT and KIT mutational status, in a series of 13 mesonephric neoplasms (5 cervical [including 2 cervical carcinosarcomas], 3 uterine corpora, 4 ovarian, and 1 vaginal/pelvic). The intensity of staining and proportion of cells showing cytoplasmic/membranous staining for c-KIT were recorded. KIT was sequenced using a next-generation sequencing panel that targeted 120 hotspots and 17 exons in 33 known actionable cancer genes. This panel included KIT exons 9, 11, and 13, and 6 hotspots (T670, D816, D820, N822, Y823, A829). Although c-KIT immunohistochemical exp...
Source: The American Journal of Surgical Pathology - Category: Pathology Tags: Original Articles Source Type: research
y-Coquard I Abstract The group of rare malignant ovarian tumors includes the group of germ cell tumors, sex cords stromal ovarian tumors, small cell carcinoma, malignant Brenner tumors, rare epithelial tumors such as mucinous carcinoma, clear cell carcinoma, or low-grade serous carcinoma, as well as ovarian carcinosarcoma. Together they comprise about 10% of all ovarian tumors. Due to their low prevalence and their heterogeneity, data and treatment recommendations are limited. Even though all ovarian tumors are staged according to the FIGO staging of epithelial ovarian tumors, treatment differs especially in germ ...
Source: Bulletin du Cancer - Category: Cancer & Oncology Authors: Tags: Bull Cancer Source Type: research
Authors: Lopez S, Perrone E, Bellone S, Bonazzoli E, Zeybek B, Han C, Tymon-Rosario J, Altwerger G, Menderes G, Bianchi A, Zammataro L, Manzano A, Manara P, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Raspagliesi F, Angioli R, Buza N, Hui P, Bond HM, Santin AD Abstract Background: Uterine and ovarian carcinosarcomas (CS) are rare cancers with poor prognosis. Sacituzumab-govitecan (SG) is a new class of antibody-drug-conjugate (ADC) targeting the human-trophoblast-cell-surface marker (Trop-2) conjugated with the active metabolite of irinotecan (SN-38). We evaluated the efficacy of SG against biologically ag...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
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...
Source: Gynecologic Oncology - Category: Cancer & Oncology Authors: Tags: Gynecol Oncol Source Type: research
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