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Keywords | DNA-methylation | breast cancer | prognosis | therapy prediction |<br />
DNA METHYLATION<br />
Epigenetic profi ling of breast cancer:<br />
prognostic and therapeutic applications<br />
Summary<br />
Breast cancer is a genetic as well as an epigenetic disease.<br />
A prominent epigenetic alteration is DNA-methylation in<br />
the promoter region of a gene that prevents the gene from<br />
being expressed. Recently, high-throughput methods to<br />
analyse the methylation status of genes in a large number<br />
of samples simultaneously have been developed. We formed<br />
the present consortium, which encompasses members of<br />
the European Union and associated Member States, to take<br />
a multidisciplinary and innovative approach to study the<br />
DNA-methylation of breast tumours in order to improve<br />
the prognosis and treatment possibilities of the patients.<br />
The participating centres are contributing complementary<br />
state-of-theart proprietary technical expertise, large and<br />
well-documented tissue resources, and intense clinical<br />
expertise.<br />
Problem<br />
Today, the choice of treatment for individual breast cancer<br />
patients is based on a number of traditional clinical and<br />
pathological determinations. Stratifi cation is not suffi cient<br />
since approximately 90 % of patients with lymph-node negative<br />
disease are grouped into a high-risk group and are<br />
consequently recommended adjuvant systemic therapy,<br />
even though it is known that only about 30 % of nodenegative<br />
patients will eventually experience disease recurrence.<br />
In addition, markers are needed that can predict<br />
which patient will respond to a specifi c type of systemic<br />
endocrine or chemotherapy, both in the adjuvant and<br />
metastatic setting.<br />
EARLY DETECTION, DIAGNOSIS AND PROGNOSIS<br />
Aim<br />
To implement the epigenetic DNA-methylation analyses in<br />
the clinical setting to benefi t both the individual patient by<br />
optimising their therapy concept, and the society as a whole<br />
by minimising treatment-related side eff ects and maximising<br />
cure rates.<br />
Expected results<br />
The achievements expected are the improvement of patient<br />
prognosis by better risk assessment, and more specifi c therapeutic<br />
approaches based on newly developed targeted<br />
therapies and better therapy selection.<br />
Potential applications<br />
Methylation-based predictive tests are highly suited for clinical<br />
routine application since the DNA-based methodology<br />
is very robust in a routine setting as they can be accurately<br />
and sensitively detected in paraffi n-embedded material.<br />
Large volume testing would be feasible for routine testing<br />
through an automated high-throughput approach.<br />
The fi fth base in the genome:<br />
Methylation of the carbon 5 position is the epigenetic modifi cation in the mammalian genome<br />
that contributes to cancer. © Epigenomics AG, Berlin.<br />
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