Loss of heterozygosity on chromosomes 7p, 7q, 9p and 11q is an early event in ovarian tumorigenesis

Watson, Richard H.; Neville, Phillippa J.; Roy, W. Qu; Hitchcock, Andrew; Campbell, Ian

doi:10.1038/sj.onc.1201945

Cited by 44 publications

(20 citation statements)

References 23 publications

(25 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Loss of heterozygosity at multiple loci has been reported to occur early in tumorigenesis in a number of cancers (Watson et al 1998;Lakhani et al 1999;Kittiniyom et al 2001). Assessment of metastatic potential will be another exciting application, as demonstrated by the recent findings that gene-dosage increases for PRL3 at 8q24.3 correlate with metastasis in colon cancer (Saha et al 2001).…”

Section: Discussionmentioning

confidence: 97%

Whole Genome Analysis of Genetic Alterations in Small DNA Samples Using Hyperbranched Strand Displacement Amplification and Array–CGH

Lage¹,

Leamon²,

Pejović³

et al. 2003

Genome Res.

233

210

View full text Add to dashboard Cite

Structural genetic alterations in cancer often involve gene loss or gene amplification. With the advent of microarray approaches for the analysis of the genome, as exemplified by array–CGH (Comparative GenomicHybridization), scanning for gene-dosage alterations is limited only by issues of DNA microarray density. However, samples of interest to the pathologist often comprise small clusters of just a few hundred cells, which do not provide sufficient DNA for array–CGH analysis. We sought to develop a simple method that would permit amplification of the whole genome without the use of thermocycling or ligation of DNA adaptors, because such a method would lend itself to the automated processing of a large number of tissue samples. We describe a method that permits the isothermal amplification of genomic DNA with high fidelity and limited sequence representation bias. The method is based on strand displacement reactions that propagate by a hyperbranching mechanism, and generate hundreds, or even thousands, of copies of the genome in a few hours. Using whole genome isothermal amplification, in combination with comparative genomic hybridization on cDNA microarrays, we demonstrate the ability to detect gene losses in yeast and gene dosage imbalances in human breast tumor cell lines. Although sequence representation bias in the amplified DNA presents potential problems for CGH analysis, these problems have been overcome by using amplified DNA in both control and tester samples. Gene-dosage alterations of threefold or more can be observed with high reproducibility with as few as 1000 cells of starting material.

show abstract

Section: Discussionmentioning

confidence: 97%

Whole Genome Analysis of Genetic Alterations in Small DNA Samples Using Hyperbranched Strand Displacement Amplification and Array–CGH

Lage¹,

Leamon²,

Pejović³

et al. 2003

Genome Res.

233

210

View full text Add to dashboard Cite

show abstract

“…One reason for this could be that FAU is located on chromosome arm 11q , which has been reported to be associated with loss of heterozygosity (LOH) (Watson et al, 1998) or chromosomal over representation (Schrami et al, 2003) in ovarian cancer. LOH at 11q has been particularly noted in the characteristically more chemotherapy-resistant ovarian clear cell carcinomas (Dent et al, 2003) and the percentage of tumors Activated caspases as a marker of caspase-dependent apoptosis were determined using the CaspaTag Pan-Caspase In Situ Assay Kit after 72-hr incubation with carboplatin.…”

Section: Discussionmentioning

confidence: 98%

FAU regulates carboplatin resistance in ovarian cancer

Moss

Mourtada-Maarabouni

Pickard

et al. 2009

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

The development of chemotherapy resistance by cancer cells is complex, using different mechanisms and pathways. The gene FAU (Finkel-Biskis-Reilly murine sarcoma virus (FBR-MuSV)-associated ubiquitously expressed gene) was identified through functional expression cloning and previous data have shown that overexpression enhances apoptosis in several cell types. We demonstrate that the expression of FAU was reduced in the A2780cis (cisplatin resistant subclone of A2780) cell line compared with the A2780 ovarian cancer cell line, and was directly related to the cell line's sensitivity to carboplatin. Downregulation of FAU in the A2780 cell line by transfection with two predesigned short-interfering RNAs (siRNAs) to FAU resulted in a significant increase in resistance to carboplatin-induced cell death. Downregulation resulted in increased cell viability and reduced apoptosis after 72 hr of drug treatment compared with the negative controls (Kruskal-Wallis P = 0.0002). Transfection of the A2780cis cell line with the pcDNA3 plasmid containing FAU was associated with increased sensitivity to carboplatin-induced apoptosis, with decreased cell viability and increased apoptosis (Mann Whitney P < 0.0001). The expression of FAU was examined by quantitative real-time reverse transcriptase polymerase chain reaction in normal and malignant ovarian tissue. A significant reduction in the expression of FAU was seen in the malignant compared with normal ovarian samples (Kruskal-Wallis P = 0.0261). These data support a role for FAU in the regulation of platinum-resistance in ovarian cancer. Further research is needed into the apoptotic pathway containing FAU to investigate the potential for targeted therapies to increase or restore the platinum sensitivity of ovarian cancer.

show abstract

“…24,25 Common denominators however, have been identified in low malignant potential and invasive ovarian carcinomas, as for example the loss of heterozygosity (LOH). 26 Our findings assign hPar1 as another common RNA from normal and invasive ovarian carcinoma specimens was reverse transcribed and amplified. FAK was detected using a set of specific primers as compared to a housekeeping control gene GAPDH.…”

Section: Discussionmentioning

confidence: 99%

Differential expression of Protease activated receptor 1 (Par1) and pY397FAK in benign and malignant human ovarian tissue samples

Grisaru‐Granovsky

Salah

Maoz

et al. 2004

Intl Journal of Cancer

103

View full text Add to dashboard Cite

Protease activated receptors (PAR) form a family of G-protein coupled receptors (GPCR) encoding their own ligands and uniquely activated via proteolytic cleavage. Although proteases in general have been implicated in the remodeling of the extracellular tumor microenvironment, the role of cell surface receptors activated by proteolysis is now emerging. In our present study we investigated the expression pattern of protease activated receptor 1 hPar1 in ovarian carcinoma tissue samples. Abundant hPar1 mRNA and protein were detected in "low malignant potential" and in invasive carcinomas, regardless of the histological subtype. In contrast, no hPar1 expression was detected on the cell surface of normal ovarian epithelium. The differential expression pattern of hPar1 was shown by in situ hybridization, immunohistochemistry and semi-quantitative RT-PCR analyses. In early stages of ovarian carcinoma (Ia), the contra lateral normal ovary showed strong PAR1 expression as opposed to the lack of expression in the ovarian epithelium obtained from normal individuals. In parallel, we analyzed the expression pattern of ␣v␤5 integrin and of activated focal adhesion kinase (FAK), a major focal contact protein, in these tissues. Although abundant expression of ␣v␤5 integrin was observed in all tissues specimens examined, regardless of either normal or malignant, the level of activated FAK was differentially expressed. Phosphorylated FAK was seen in invasive ovarian carcinoma, but not in the normal ovarian epithelium. The abundant hPar1 levels in pathological malignant ovarian carcinoma is likely to transmit signals leading to the phosphorylation of FAK and thereby alterations in the integrin functional state. Altogether our data suggest that hPar1 and FAK cooperate to promote ovarian cancer malignancy.

show abstract

Loss of heterozygosity on chromosomes 7p, 7q, 9p and 11q is an early event in ovarian tumorigenesis

Cited by 44 publications

References 23 publications

Whole Genome Analysis of Genetic Alterations in Small DNA Samples Using Hyperbranched Strand Displacement Amplification and Array–CGH

Whole Genome Analysis of Genetic Alterations in Small DNA Samples Using Hyperbranched Strand Displacement Amplification and Array–CGH

FAU regulates carboplatin resistance in ovarian cancer

Differential expression of Protease activated receptor 1 (Par1) and pY397FAK in benign and malignant human ovarian tissue samples

Contact Info

Product

Resources

About