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DNA Chips Improve Brain Tumour Diagnosis

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A team of scientists from the Institut Curie and Inserm have announced that they have harnessed the technology of DNA chips that were able to distinguish the tumours with the best prognosis, whose chromosome 1 has undergone a specific deletion.

The scientists anticipate that screening for these deletions could be incorporated into standard diagnostic tests by the end of 2005.

Results, published in the September 2005 issue of Annals of Neurology, were obtained by studying the specific genetic alterations of a subgroup of more chemosensitive gliomas.

Jean-Yves Delattre and his team at the Pitie-Salpetriere Hospital and Olivier Delattre and his team at the Institut Curie identified several types of deletions of chromosome 1, only one of which is associated with gliomas with a good prognosis.

These findings were recorded using array CGH analysis; a technique that can establish high-resolution maps revealing genome anomalies (amplifications, deletions).

Only the complete loss of the short arm of chromosome 1 combined with complete loss of the long arm of chromosome 19 signifies a good prognosis.

Partial loss of the short arm of chromosome 1, on the other hand, characterised more aggressive tumours.

This retrospective study was done with samples from the tumour library of the Pitie-Salpetriere Hospital using a technology developed at the Institut Curie.

The findings suggest that the genes involved in these two deletions, and hence associated with gliomas of good and poor prognosis, are different.

The report stated that genomics and notably DNA chips generated information on the alterations underlying cancers.

In using these tools, physicians can revamp and refine tumour classification to enable more individualised treatments.

According Frost and Sullivan, drugs that address rising multifactoral disorders such as cancer as well as lifestyle disorders such as obesity are also likely to experience strong revenue growth.

Moreover, as patient groups become more fragmented and diagnostic methods improve, the demand for evidence-based personalised treatments are likely to increase.

CGH chips - array CGH - are made using targets from genome fragments of about 150 000 base pairs. With some 3 500 targets, these chips afford an overview of the whole genome.

In practical terms, tumour DNA and normal DNA labelled with fluorescent molecules of different colours (red and green for instance) are spread on the chip.

These two types of DNA (probes) hybridise with the targets on the chip, resulting in the appearance of luminescent spots.

The relation between the two types of fluorescence is analysed using software, which determines the relative quantity of each probe.

When red predominates, there is an excess of tumour DNA: the region considered has been amplified.

When green is preponderant, only normal DNA has bound: this region has been deleted from the tumour DNA.

When the two colours are present in equal amount, the tumour DNA has neither gained nor lost this region and the probe appears yellow.