This article is more than 5 years old. Information may no longer be current.
Novel epigenetic phenotype of bladder tumors may have been discovered
Vallot C. J Natl Cancer Inst. 2011;103:1-14.
Click Here to Manage Email Alerts
A multiple regional epigenetic silencing phenotype of bladder tumor characterized by the silencing of several chromosomal regions has been identified, according to study findings.
Researchers from several institutions in France analyzed RNA from 57 bladder tumors and compared those results with those from normal urothelium. The researchers used Affymetrix microarrays and real-time quantitative polymerase chain reaction to search for chromosomal regions affected by epigenetic silencing in cancer.
Verification of epigenetic silencing was achieved using gene re-expression after the treatment of bladder cell lines with 5-aza-deoxycytidine and trichostatin A. The researchers used bisulfite sequencing and histone methylation to study DNA methylation; they used chromatin immunoprecipitation to study acetylation.
Tumors with multiple regional epigenetic silencing were distinguished from those without by clustering software. The association of the multiple regional epigenetic silencing phenotype with histopathologic and molecular types of bladder cancer also was explored by clustering.
A second panel of 40 tumor samples was used to confirm the results of the initial analysis. The secondary results were extended in vitro with seven bladder cancer cell lines.
An epigenetic mechanism silenced seven chromosomal regions of contiguous genes, according to the results. No associations between epigenetic silencing and DNA methylation were observed. However, the researchers observed associations between epigenetic silencing and histone H3K9 and H3K27 methylation and histone H3K9 hypoacetylation.
A subgroup of 26 tumors was also examined. In this group, all seven chromosomal regions were concordantly silenced, which the researchers said defined a multiple regional epigenetic silencing phenotype. They noted that these tumors exhibited a carcinoma in situ-associated gene expression signature in 25 of these 26 tumors; by comparison, zero of 31 tumors that were not multiple regional epigenetic silencing phenotype did not exhibit this gene expression (P<10–14).
These same tumors also carried FGFR3 mutations at a rate of one of 26, compared with 22 of 31 nonmultiple regional epigenetic silencing phenotype tumors, (P<10–6), and contained 76% of the muscle-invasive tumors, according to the results.
“Cell lines derived from aggressive bladder tumors presented epigenetic silencing of the same regions,” the researchers wrote.
This type of work is indicative of where the field of solid tumor translational research is going. That is, it looks for specific genetic events, in this case gene silencing via methylation, that may influence tumor biology. Although this report is preliminary in a small number of pts, eventually we would like to use such an analysis to profile individual tumors to chose specific therapies, or to better prognosticate outcome with information that adds value to standard clinical and pathologic variables.
– Brian I. Rini, MD
Department of Solid Tumor Oncology,
Cleveland Clinic Taussig Cancer Institute
Disclosures: Dr. Rini reports consulting and research support from Pfizer, GSK.
 |
Follow HemOncToday.com on Twitter. |