A Genomic Signature Of 254 Genes Predicting Clinical Outcome In Primary Cutaneous Melanoma Identified

Main Category: Melanoma / Skin Cancer
Also Included In: Dermatology;  Genetics
Article Date: 06 Apr 2006 - 0:00 PDT

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EORTC Melanoma Group researchers have identified a genomic signature predicting clinical outcome in Primary Cutaneous Melanoma, after patients having undergone standard treatment. The results of the retrospective study are published in today's issue of the Journal of the National Cancer Institute.

(EORTC = European Organisation for Research and Treatment of Cancer)

About the study:

The study was initiated on the following observation: Patients with Primary Cutaneous Melanoma having received standard treatment fall into two groups - one group of patients without relapse after four or more years, and another group which recurrently develops metastasis.

Micro-array analysis allowed to isolate a set of 254 genes which are expressed differently in the tumor with good prognosis than in the tumor with bad prognosis. These 254 genes represent a "genomic signature" of the tumor which allows to identify to which of the two groups of prognosis a patient belongs to.

Some of the genes in question have a known activity in melanoma, whereas other genes identified have also been previously shown to be involved in other cancers. Of particular interest are 33 genes in melanomas from patients that did not metastasize - indicating an anti-metastatic role for these genes.

Furthermore, a biological pathway associated with the expression of these genes was identified: Two proteins where shown to intervene in the process of DNA replication. These two proteins (helicasis) represent potential targets for the development of new therapies for the patients that fall within the group with bad prognosis.

The findings allow for a more accurate diagnosis of melanoma and will allow patients to make a more informed choice as to whether or not to take part in clinical trials. For a patient with bad prognosis, taking part in a clinical trial could possibly result in an increase chances of survival or/and quality of life.

The study is the first study that uses a large retrospective series of frozen samples with long-term follow-up to analyze the genes underlying progression in melanoma. Gene expression profiling data is still scarce because of the lack of retrospective collections of frozen tumors.

European Partners:

These findings result from European research collaboration between:

-- leading European experts in the field of melanoma research working within EORTC Melanoma group

-- several hospitals in Europe creating the largest international biobank in Primary Cutaneous Melanoma (France: Institut Gustave Roussy (IGR), Villejuif, Belgium: Gasthuisberg University Hospital, Leuven, Spain: Spanish National Cancer Centre (CNIO), Madrid) 1

-- a technology platform providing the necessary technology and know-how for the study of gene-expression (Functional Genomics Platform, Institut Gustave Roussy (IGR), Villejuif).

About Melanoma:

The main cause for a Primary Cutaneous Melanoma is due to the skin being exposed to UV radiation A and especially B. As of today, no drug which could ensure complete recovery from Primary Cutaneous Melanoma is available. Prevention against skin cancer is therefore of crucial importance. However, the above mentioned findings give rise to the hope that research in the field will progress.

About EORTC Created in 1962, the European Organisation for Research and Treatment of Cancer (EORTC) is a not-for-profit international cancer research organisation under the Belgian Law.

EORTC has the mission to develop, conduct, coordinate and stimulate laboratory and clinical research in Europe to improve the management of cancer and related problems by increasing survival but also patients' quality of life. The ultimate goal of the EORTC is to improve the standard of cancer treatment in Europe, through the development of new drugs and other innovative approaches, and to test more effective therapeutic strategies, using drugs which are already commercially available, or surgery or radiotherapy. EORTC has the aim to facilitate the passage of experimental discoveries into state-of-the-art treatment by keeping to a minimum the time lapse between the discovery of new anti-cancer agents and the implementation of their therapeutic benefit for patients with cancer.

EORTC promotes multidisciplinary cancer research in Europe and is linked to other leading biomedical research organisations around the world. EORTC research takes place in over 300 hospitals, universities and cancer centers in 32 countries and the unique network of investigators of EORTC comprises more than 2000 clinicians collaborating on a voluntary basis in over 20 multidisciplinary groups.

EORTC
Avenue E. Mounier 83/11
B - 1200 Brussels / Belgium
http://www.eortc.be

1. A biobank may be defined as "a collection of samples of human bodily substances � that is associated with personal data and information on their donors" (German National Ethics Council, Biobanks for Research, Mar 17 2004, p. 7). Biobanks for research constitute an important resource for identifying the causes and mechanisms of diseases, and hold the prospect to lead to significant breakthroughs especially in translational cancer research.