DNA chips improve brain tumour diagnosis

Current methods of treating brain tumours are a difficult and painstaking process because of their heterogeneity and variable malignancy. Gliomas are the most frequent brain tumours in adults and diagnosis is essentially based on subtle microscopic characteristics presenting problems.

There is no specific marker or genetic signature, and the present classification seems inadequate in predicting the outcome of each type of glioma.

The team of scientists from the Institut Curie and Inserm 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 Pitié-Salpêtrière 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 Pitié-Salpêtrière 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. In addition, use of the array CGH technique should improve the diagnosis of gliomas and their treatment.

The report stated that genomics and notably DNA chips generated new information on the alterations underlying cancers. In using these tools, physicians can revamp and refine tumour classification to enable more individualised treatments.

Pharmacogenetics, tailoring drug treatments to a person's genetic profile is said to be the future of drug research and development, paving the way for individualised treatment on an unprecedented scale.

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.

One of these diagnostic methods is Comparative Genomic Hybridisation (CGH), which allows global analysis of the genome.

It is a tool to identify genome regions that have been amplified or deleted - very frequent events in tumour cells. CGH combines the techniques of cytogenetics and DNA chips.

New 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.