A genomic signature of 254 genes predicting clinical outcome in Primary Cutaneous Melanoma identified

Apr 6 2006

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.

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.

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