Cancer Research - Europa

Keywords | DNA-methylation | breast cancer | prognosis | therapy prediction |
DNA METHYLATION
Epigenetic profi ling of breast cancer:
prognostic and therapeutic applications
Summary
Breast cancer is a genetic as well as an epigenetic disease.
A prominent epigenetic alteration is DNA-methylation in
the promoter region of a gene that prevents the gene from
being expressed. Recently, high-throughput methods to
analyse the methylation status of genes in a large number
of samples simultaneously have been developed. We formed
the present consortium, which encompasses members of
the European Union and associated Member States, to take
a multidisciplinary and innovative approach to study the
DNA-methylation of breast tumours in order to improve
the prognosis and treatment possibilities of the patients.
The participating centres are contributing complementary
state-of-theart proprietary technical expertise, large and
well-documented tissue resources, and intense clinical
expertise.
Problem
Today, the choice of treatment for individual breast cancer
patients is based on a number of traditional clinical and
pathological determinations. Stratifi cation is not suffi cient
since approximately 90 % of patients with lymph-node negative
disease are grouped into a high-risk group and are
consequently recommended adjuvant systemic therapy,
even though it is known that only about 30 % of nodenegative
patients will eventually experience disease recurrence.
In addition, markers are needed that can predict
which patient will respond to a specifi c type of systemic
endocrine or chemotherapy, both in the adjuvant and
metastatic setting.
EARLY DETECTION, DIAGNOSIS AND PROGNOSIS
Aim
To implement the epigenetic DNA-methylation analyses in
the clinical setting to benefi t both the individual patient by
optimising their therapy concept, and the society as a whole
by minimising treatment-related side eff ects and maximising
cure rates.
Expected results
The achievements expected are the improvement of patient
prognosis by better risk assessment, and more specifi c therapeutic
approaches based on newly developed targeted
therapies and better therapy selection.
Potential applications
Methylation-based predictive tests are highly suited for clinical
routine application since the DNA-based methodology
is very robust in a routine setting as they can be accurately
and sensitively detected in paraffi n-embedded material.
Large volume testing would be feasible for routine testing
through an automated high-throughput approach.
The fi fth base in the genome:
Methylation of the carbon 5 position is the epigenetic modifi cation in the mammalian genome
that contributes to cancer. © Epigenomics AG, Berlin.
121