New England Journal of Medicine Publication!

TFAP2E gene hypermethylation associated with clinical non-responsiveness to chemotherapy in colorectal cancer

In many cancers different patterns of DNA methylation (epigenetics) appear likely to discriminate aggressive versus nonaggressive disease and to predict responsiveness to specific treatments.
A new study led by Prof Matthias Ebert and Dr Marc Taenzer (University Hospital Mannheim and Technical University, Munich, Germany) and collaborators based in Germany and Dr David Hughes at the Centre for Systems Medicine in the RCSI has found that an epigenetic change common in colorectal cancer predicts poor response to chemotherapy.
The study published in the January 5th 2012 edition of the New England Journal of Medicine* shows that TFAP2E gene hypermethylation (i.e., highly methylated gene sequences) was associated with clinical non-responsiveness to chemotherapy in colorectal cancer.

The researchers collected samples from patients undergoing surgery or chemotherapy for colorectal cancer at six German university hospitals. In the initial cohort of 74 patients whose tumour DNA was analyzed, 38 showed TFAP2E hypermethylation (51%), which didn’t correlate with tumor site, grade, stage, or any other common clinical or pathological characteristics. In four cohorts totalling 220 colorectal patients treated with fluorouracil-based chemotherapy or chemoradiation through different clinical trials TFAP2E epigenetic alteration was associated with significantly lower tumour response rates.

*Ebert MPA, Taenzer M, Balluff B, Burgermeister E, Kretzschmar AK, Hughes DJ, Tetzner R, Lofton-Day C, Rosenberg R, Reinacher-Schick A, Schulmann K, Hofheinz R, Roecken C, Keller G, Langer R, Stoehlmacher J, Schuster T, Stroebel P, Schmid R (2012) TFAP2E/DKK4 and Chemoresistance in Colorectal Cancer. New England Journal of Medicine, 366, 44-53.

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