In the July 15th issue of Cancer Research (Impact factor 7.6) Jo Anders Rønneberg (photo) - a PhD fellow in the group of Cancer Genome variation - published a paper entitled "GSTP1 promoter haplotypes affect DNA methylation levels and promoter activity in breast carcinomas".
The authors show that the level of DNA methylation of the GSTP1 promoter is affected by the haplotype structure in the region and may influence survival.
Functional analyses were performed employing EMSA, siRNA and Luciferase reporter vectors to show that the promoter haplotypes respond differentially to the transcription factor Myb in breast cancer cell-lines and this response is dependent on the cell type (basal vs luminal-like), the Myb dependent induction being most marked in the basal like cell type. Linear regression analysis showed that the promoter DNA methylation was most strongly associated to the haplotype when compared to other known factors influencing DNA methylation like the estrogen receptor status of the tumor. The report was in collaboration with the IMBV at the University of Oslo, Haukeland University Hospital in Bergen and Centre National de Genotypage in Evry, France.
The Cancer Genome variation group at the Department of Genetics is studying how genetic variation (SNPs and CNVs) affects the phenotype in breast tumors with the aim of identifying predictive markers for treatment response and prognosis. The group is headed by Professor Vessela N. Kristensen.
Rønneberg JA, Tost J, Solvang HK, Alnaes GI, Johansen FE, Brendeford EM, Yakhini Z, Gut IG, Lønning PE, Børresen-Dale AL, Gabrielsen OS, Kristensen VN.
GSTP1 promoter haplotypes affect DNA methylation levels and promoter activity in breast carcinomas.
Cancer Res. 2008 Jul 15;68(14):5562-71.