Establishment and molecular characterization of a human ovarian clear cell carcinoma cell line (FDOV1)

Ouyang

et al. 2023

IJMS

Self Cite

Peritoneal implantation and lymph node metastasis have different driving mechanisms in ovarian cancer. Elucidating the underlying mechanism of lymph node metastasis is important for treatment outcomes. A new cell line, FDOVL, was established from a metastatic lymph node of a patient with primary platinum-resistant ovarian cancer and was then characterized. The effect of NOTCH1-p.C702fs mutation and NOTCH1 inhibitor on migration was evaluated in vitro and in vivo. Ten paired primary sites and metastatic lymph nodes were analyzed by RNA sequencing. The FDOVL cell line with serious karyotype abnormalities could be stably passaged and could be used to generated xenografts. NOTCH1-p.C702fs mutation was found exclusively in the FDOVL cell line and the metastatic lymph node. The mutation promoted migration and invasion in cell and animal models, and these effects were markedly repressed by the NOTCH inhibitor LY3039478. RNA sequencing confirmed CSF3 as the downstream effector of NOTCH1 mutation. Furthermore, the mutation was significantly more common in metastatic lymph nodes than in other peritoneal metastases in 10 paired samples (60% vs. 20%). The study revealed that NOTCH1 mutation is probably a driver of lymph node metastasis in ovarian cancer, which offers new ideas for the treatment of ovarian cancer lymph node metastasis with NOTCH inhibitors.

Section: Methodsmentioning

confidence: 99%

“…BRCA1 and NOTCH1 mutations in cells were confirmed by Sanger-sequencing, as described in a previous study [ 32 ].…”

Section: Methodsmentioning

confidence: 99%

A NOTCH1 Mutation Found in a Newly Established Ovarian Cancer Cell Line (FDOVL) Promotes Lymph Node Metastasis in Ovarian Cancer

Ouyang

et al. 2023

IJMS

Self Cite

“…And in a further step, a total of 34 established cell lines were used to decode potential therapeutic targets specific for HGSOC [18,19]. In addition, cell lines for ovarian clear cell carcinoma (CCC) [20], low-grade serous ovarian carcinoma (LGSOC) [21], endometrioid adenocarcinoma (EMC) [22], and other pathology were cultured and introduced by researchers worldwide.…”

Section: Conventional Cell Linesmentioning

confidence: 99%

Harnessing preclinical models for the interrogation of ovarian cancer

Qin

Fan

Lü

et al. 2022

J Exp Clin Cancer Res

Ovarian cancer (OC) is a heterogeneous malignancy with various etiology, histopathology, and biological feature. Despite accumulating understanding of OC in the post-genomic era, the preclinical knowledge still undergoes limited translation from bench to beside, and the prognosis of ovarian cancer has remained dismal over the past 30 years. Henceforth, reliable preclinical model systems are warranted to bridge the gap between laboratory experiments and clinical practice. In this review, we discuss the status quo of ovarian cancer preclinical models which includes conventional cell line models, patient-derived xenografts (PDXs), patient-derived organoids (PDOs), patient-derived explants (PDEs), and genetically engineered mouse models (GEMMs). Each model has its own strengths and drawbacks. We focus on the potentials and challenges of using these valuable tools, either alone or in combination, to interrogate critical issues with OC.

“…39,40 Tumors of some origins such as thyroid, cervical, ovarian, bone and neurologic cancers have not yet well-investigated for this molecular alteration. [39][40][41] Overall, SPOP mutations in gynecological malignancies is not uncommon as some studies found these molecular alterations in 18% of endometrial CCCs 35, 42, 11% of ovarian CCCs 40 , up to 8% of endometrial serous carcinomas 35 and 14% of Müllerian carcinosarcomas 43 . Although functional studies of SPOP in gynecological malignancies are limited, it has been suggested that SPOP mutations can be targeted with DNA damaging agents such as PARP inhibitor as studied in prostate carcinomas.…”

Section: Next Generation Sequencing (Ngs) Characteristicsmentioning

confidence: 99%

Clear Cell Carcinoma of Uterine Cervix: A Clinicopathologic Review and Molecular Characterization

Pakbaz

Esfahanian

Sanii

et al. 2022

Preprint

Clear cell carcinoma of uterine cervix (CCCUC) is an uncommon variant of cervical adenocarcinoma unrelated to Human Papilloma Virus (HPV). With widespread Pap test screening and HPV vaccination resulting decline in incidence of cervical HPV-related cancers, it is important to develop better understanding of the less common HPV-independent variants of cervical adenocarcinoma, including CCCUC. In this study, 10 cases of CCCUCs diagnosed over a 15 year period were retrospectively reviewed for clinicopathological and immunohistochemistry characteristics and HPV DNA PCR; and next generation sequencing (NGS) was performed in cases with available pathology material. Mean age of patients was 39.6 (range of 18–82) and all presented with vaginal bleeding. Most cases (6/10) were diagnosed at FIGO stage IIB. Eight patients had surgery, with lymph nodes dissection in 7. Adjuvant therapy followed in 5 cases. Median follow up period was 38 months. HPV DNA PCR proved negative HPV status in all cases. For immunohistochemistry, all cases showed wild-type p53 expression, positive PAX8 and HNF1β, and negative ER and PR. MMR protein expression was intact in 4 cases. Two cases had lost/equivocal MSH2/MSH6 expression, one of which proved negative for microsatellite instability in NGS. Based on combined positive score (CPS), more than half of cases with available PD-L1 (4/7) were positive. 70 genetic variants were identified in testing of tumor tissue DNA from 6 cases with an NGS panel assessing 562 cancer-associated genes for single-nucleotide and copy-number variations for selected genes, and insertions/deletions. Variants occurred most frequently in genes ATM, CDH23, CSMD3, KDM5C, LRP1B, NIN, PKHD1, and RNF213. Pathways that were enriched for genes in this data set include apoptosis regulation, cell cycle and DNA repair, PI3K-AKT signaling, and NGF signaling. Multiple genes were associated with receptor tyrosine kinase activity, chromatin remodeling, and transcriptional regulation. This is the first study to explore the genomic landscape of CCCUC using Next Generation Sequencing. Some potentially actionable molecular alterations are present in these tumors. However, genetic findings are heterogeneous and further studies with larger sample size is required to better characterize this rare malignancy and to allow development of novel diagnostic and therapeutic techniques.