Characterization of 10 vulvar carcinoma cell lines by karyotyping, comparative genomic hybridization and flow cytometry
Cancer Genetics Research, Department of Otolaryngology, Henry Ford Health System, Detroit, MI 48202, USA. Gynecologic Oncology
(Impact Factor: 3.77).
05/2004; 93(1):155-63. DOI: 10.1016/j.ygyno.2003.12.033
Ten vulvar squamous cell carcinoma cell lines established at the University of Michigan (UM-SCV-1A, -1B, -2, -3, -4, -6, -7) and at the University of Turku (UT-SCV-1, -2, -3) were characterized by G-banding karyotyping, comparative genomic hybridization (CGH), and deoxyribonucleic acid (DNA) flow cytometry.
All cell lines had hyperdiploid DNA content as measured by flow cytometry. The DNA index (DI) remained relatively stable through different passages in 9 of 10 cases. DIs of UM-SCV-3 and UT-SCV-2 were near-diploid, as were the corresponding karyotypes. The 10 SCVs showed remarkable genetic similarities with respect to consistent chromosome rearrangements. Loss of 3p, noted in 8/10 SCVs, was narrowed to the smallest common region at 3p11-3p13. Loss of 8pter-p11 was observed in 10/10 cell lines. Loss of 11qter-q23 was present in UM-SCV-1 and -2, and in all four recently karyotyped SCVs. Other consistent losses include Xpter-p11 in 6/10, and 18qter-q11 in 7/10 cell lines. Common gains included gain of 8q in 8/10 and 3q in 6/10. Consistent copy number imbalances were confirmed by CGH; concerning loss of 3p, in 63%, to loss of 8p in 70%, to gain of 3q in 83%, and to gain of 8q in 75% of the cell lines.
CGH and karyotyping showed concordance in defining copy number imbalances, thus supporting the accuracy of CGH to detect chromosome imbalances in tumors that cannot be karyotyped.
Available from: Ned Powell
- "However, there are currently no licensed topical treatments for VIN, and development of such treatments has been hampered by the absence of relevant in vitro models. While there are numerous cell lines derived from vulval carcinomas [Raitanen et al., 2004], we are only aware of a single report describing culture of vulval intraepithelial neoplasia [Grassmann et al., 1996]. Mechanistic studies of molecules under investigation in clinical trials (e.g., Cidofovir [Tristram and Fiander, 2009]) have therefore been based primarily on immortal cell lines derived from more aggressive and metastatic tumors, which may have limited relevance to early stage neoplastic conditions like vulval intraepithelial neoplasia [Andrei et al., 1998; Andrei et al., 2000; Abdulkarim et al., 2002]. "
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ABSTRACT: Vulval intraepithelial neoplasia is a precursor of vulval cancer and is commonly caused by infection with Human Papillomavirus (HPV). Development of topical treatments for vulval intraepithelial neoplasia requires appropriate in vitro models. This study evaluated the feasibility of primary culture of vulval intraepithelial neoplasia biopsy tissue to produce cell lines for use as in vitro models. A potentially immortal cell line was produced which gave rise to three monoclonal lines. These lines were characterized for HPV genomic integration and for viral gene expression using ligation-mediated PCR and quantitative PCR. Distinct patterns of viral integration and gene expression were observed among the three lines. Integration and expression data were validated using deep sequencing of mRNA. Gene ontology analyses of these data also demonstrated that expression of the HPV16 E4 and E5 proteins resulted in substantial changes in the composition of the cell membrane and extracellular space, associated with alterations in cell adhesion and differentiation. These data illustrate the diverse patterns of HPV gene expression potentially present within a single lesion. The derived cell lines provide useful models to investigate the biology of vulval intraepithelial neoplasia and the interactions between different HPV gene products and potential therapeutic agents. J. Med. Virol. © 2014 Wiley Periodicals, Inc.
Journal of Medical Virology 09/2014; 86(9). DOI:10.1002/jmv.23994 · 2.35 Impact Factor
Available from: Toshiyasu Taniguchi
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ABSTRACT: Fanconi anaemia (FA) is a chromosomal instability disorder associated with a high risk of acute myeloid leukaemia (AML). Previous work has shown that the AML cell line CHRF-288, derived from a sporadic AML-M7 patient, does not express FANCF protein and exhibits a cellular FA phenotype. We show that this phenotype is corrected by a FANCF-expressing plasmid and that the absence of FANCF protein is explained by hypermethylation of the promoter region of the FANCF gene. As FANCF is localized in a hot-spot region for somatic hypermethylation (11p15), FANCF silencing might be an early step in sporadic carcinogenesis, including leukaemogenesis.
British Journal of Haematology 12/2003; 123(3):469-71. DOI:10.1046/j.1365-2141.2003.04640.x · 4.71 Impact Factor
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ABSTRACT: Chromosome rearrangements in squamous cell carcinoma of the vulva (SCV) have indicated common consistent regions of loss and gain. The overall aim of our research was to define and characterize individual genes that underlie the pathogenesis of SCV. Thirteen cell lines from 12 SCV patients were evaluated for loss and gain of 122 genes distributed throughout the genome. Individual genes were analyzed for genetic alterations using a novel genomewide strategy, the multiplex ligation-dependent probe amplification assay. Our candidate gene approach identified several altered loci. Most frequent was the loss of 1 copy of TMSB10, observed in 11 of 12 SCV patients, followed by loss of CTNNB1 and BCL2, which occurred in 7 of 12 patients. Frequent gains/amplifications included CCND1, observed in 8 of 12 patients, and IL12A, in 7 of the 12 patients. Loss and gain of specific genes observed in our study were generally concordant with the results of previous studies of cytogenetics and CGH utilizing the same SCV cell lines. Genetic alterations are hallmarks of tumorigenesis, and there is wide agreement that recurrent altered genomic loci contain genes important for tumor development and progression. Understanding the interplay of cancer genes and the pathways they utilize can lead to the detection of novel molecular targets in the diagnosis, prognosis, and treatment of SCV.
Genes Chromosomes and Cancer 10/2005; 44(2):185-93. DOI:10.1002/gcc.20230 · 4.04 Impact Factor
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