This has been shown in research in which doctor Jaime Gállego Pérez de Larraya, specialist at the Neurology Department of the University Hospital of Navarra participated. The principal objective of the study was to be able to establish the certain diagnosis of a glioma through blood analysis. The conclusions of the research have recently been published in Neurology, the official scientific publication of the American Academy of Neurology.
For the research, directed by Marc Sanson, specialist at the Neurological Service in the Mazarin del Pitié-Salpêtrière Hospital Group in Paris, free plasmatic DNA was extracted and analysed from 31 individuals without the illness and from 80 patients with glioma. The latter group had previously been tested for the state of mutation of the tumoural tissue.
The conclusion drawn confirms the possibility of detecting the IDH1 gene mutation in the plasma of patients with gliomas and, thereby, of making the diagnosis in a non-invasive manner, “a highly valuable aspect, especially amongst those patients where it is not possible to undertake a biopsy”, explained the specialist from the University Hospital. Moreover, he pointed out that, “Currently, the suspected diagnosis made using neuroimages can only be definitively confirmed with the microscopic study of a sample from the tumoural tissue itself, undertaken by a pathologist and where surgery on the patient is required”.
Given that the surgical extirpation of the damaged tissue moreover means a primary and important therapeutic procedure, in practice, the plasma analysis will facilitate non-invasive diagnosis and monitoring “amongst those patients with tumours who, due to inaccessible location or because of a very deteriorated general state, cannot be subjected to a surgical operation”, pointed out doctor Gállego. In those cases, the possibility of a diagnosis by non-surgical means will at least enable these patients to be given the necessary radiotherapy and chemotherapy treatment.
Tumoural DNA in blood
The hypothesis that the scientists considered for the research was based on the premise that tumoural cells release tumoural DNA to the blood stream. The most probable cause of this phenomenon is in the rupturing of the cells, in their destruction, and which causes their DNA to be incorporated into the blood stream. The scientists participating in the research worked with the knowledge of the existence of mutations – in the genetic code of the tumour cells – highly specific for certain tumours and which can be used as diagnostic and prognostic markers. “In the case of gliomas, in order to find a good, non-invasive marker, the ideal mutation would have to very frequent, specific (its detection being able to be translated into the existence of glioma), being able to be always located in a very concrete place in order to be able to study at this location at all times, and have diagnostic and prognostic transcendence”, explained the neuro-oncologist. And this mutation actually exists in the glioma – the mutation of the IDH1 gene which, as the specialist stresses, complies with the three mentioned conditions.
“It is a highly frequent mutation which already affects 40% of all gliomas. It should be pointed out that gliomas are classified in different grades. In what are known as low-grade (slow or relatively slow growing), the IDH1 gene mutation appears in between 75 and 80% of the cases; grade 3 (the most aggressive) is present in between 55 and 60%, which means that it continues to be frequent”, he stated.
Nevertheless, with the higher degrees of malignancy, the glioblastomas (grade 4), the percentage of the mutation presence drops to 5%.
High diagnostic precision and prognostic value
From the diagnostic point of view, having this mutation and a brain injury implies that this tumour is glial, i.e. that it is highly specific for the glioma. “It thus involves a mutation which, if detected, enables us to establish a diagnosis, given that there are no other brain tumours, other than the glioma, that are linked to this mutation”, he stated. Besides its diagnostic value, this mutation has an important prognostic value, “its presence is linked to more favourable progress”.
Thus, the IDH1 gene mutation used as a biomarker complies with three conditions: it is very frequent in gliomas; it is always located in the same genomic place; and it has a highly important diagnostic and prognostic involvement. “Detecting it means that this person has a glioma and that the prognosis is relatively better than when this type of tumour appears without the mutation”, revealed the specialist.
Challenge: overcoming technical limitations
Nonetheless, the technique analysed still has limitations the solution to which is the main challenge for future studies. The research showed that the procedures used for the detection of the mutation itself of the glioma, has a sensitivity of 60% and a specificity of 100% (meaning that no false-positive result is produced). “That is”, argued the expert, “when we detected the mutation in patients with a brain tumour, it was because this mutation really existed and, thereby, we did not err when stating these patients had a glioma”. However, he admitted, “the sensitivity of the technique is still low. It is calculated at about 60%, i.e. false negatives exist, or, in other words, in some patients with the mutation we have not been able to detect it”.
This is currently the greatest limitation to the non-invasive technique employed in the analysis of plasma. This is why the specialist is very clear that the current goal focuses on “perfecting the procedure by which, whenever the mutation exists, we are able to detect it”. The specific mutation of the glioma was discovered only 5 years ago. “This finding was a landmark in neuro-oncology and, with this work, we have shown that this mutation is detectable in blood and that, whenever it is detected, the patient has a glioma”, concluded doctor Gállego.
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