Type-Specific Cell Line Models for Type-Specific Ovarian Cancer Research

OVARIAN CARCINOMAS CONSIST OF AT LEAST FIVE DISTINCT DISEASES: high-grade serous, low-grade serous, clear cell, endometrioid, and mucinous. Biomarker and molecular characterization may represent a more biologically relevant basis for grouping and treating this family of tumors, rather than site of o...

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Veröffentlicht in:PloS one Jg. 8; H. 9; S. e72162
Hauptverfasser: Anglesio, Michael S., Wiegand, Kimberly C., Melnyk, Nataliya, Chow, Christine, Salamanca, Clara, Prentice, Leah M., Senz, Janine, Yang, Winnie, Spillman, Monique A., Cochrane, Dawn R., Shumansky, Karey, Shah, Sohrab P., Kalloger, Steve E., Huntsman, David G.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Public Library of Science 04.09.2013
Public Library of Science (PLoS)
Schlagworte:
Analysis
Biology
Biomarkers
Biotechnology
Cancer
Cancer research
Carcinoma, Ovarian Epithelial
Cell culture
Cell Line, Tumor
Chemotherapy
Copy number
Cystadenocarcinoma, Serous - genetics
Cystadenocarcinoma, Serous - pathology
Endometrial cancer
Female
Genomic analysis
Genomics
Histology
Humans
Identification methods
Laboratories
Medical research
Medicine
Mutation
Neoplasms, Glandular and Epithelial - genetics
Neoplasms, Glandular and Epithelial - pathology
Ovarian cancer
Ovarian carcinoma
Ovarian Neoplasms - genetics
Ovarian Neoplasms - pathology
p53 Protein
Pathology
Quality
Studies
Tumor cell lines
Tumor proteins
Tumor Suppressor Protein p53 - genetics
Tumors
Vancouver British Columbia Canada
Canada
ISSN:1932-6203, 1932-6203
Online-Zugang:Volltext
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Zusammenfassung:OVARIAN CARCINOMAS CONSIST OF AT LEAST FIVE DISTINCT DISEASES: high-grade serous, low-grade serous, clear cell, endometrioid, and mucinous. Biomarker and molecular characterization may represent a more biologically relevant basis for grouping and treating this family of tumors, rather than site of origin. Molecular characteristics have become the new standard for clinical pathology, however development of tailored type-specific therapies is hampered by a failure of basic research to recognize that model systems used to study these diseases must also be stratified. Unrelated model systems do offer value for study of biochemical processes but specific cellular context needs to be applied to assess relevant therapeutic strategies. We have focused on the identification of clear cell carcinoma cell line models. A panel of 32 "ovarian cancer" cell lines has been classified into histotypes using a combination of mutation profiles, IHC mutation-surrogates, and a validated immunohistochemical model. All cell lines were identity verified using STR analysis. Many described ovarian clear cell lines have characteristic mutations (including ARID1A and PIK3CA) and an overall molecular/immuno-profile typical of primary tumors. Mutations in TP53 were present in the majority of high-grade serous cell lines. Advanced genomic analysis of bona-fide clear cell carcinoma cell lines also support copy number changes in typical biomarkers such at MET and HNF1B and a lack of any recurrent expressed re-arrangements. As with primary ovarian tumors, mutation status of cancer genes like ARID1A and TP53 and a general immuno-profile serve well for establishing histotype of ovarian cancer cell We describe specific biomarkers and molecular features to re-classify generic "ovarian carcinoma" cell lines into type specific categories. Our data supports the use of prototype clear cell lines, such as TOV21G and JHOC-5, and questions the use of SKOV3 and A2780 as models of high-grade serous carcinoma.
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Conceived and designed the experiments: MSA SEK DGH. Performed the experiments: MSA KCW CS CC JS WY NM LMP. Analyzed the data: MSA KS SEK. Contributed reagents/materials/analysis tools: MSA KCW DGH SPS MAS DRC. Wrote the paper: MSA SEK DRC LMP KCW MAS DGH.
Competing Interests: The authors have declared that no competing interests exist.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0072162