By studying the familial forms of this tumor, the researchers also conclude that ALK is a gene that predisposes to neuroblastoma. This discovery may allow the development of new treatments in neuroblastomas.
It may also enable the identification in at-risk families of children who carry an altered ALK gene, so that they can be offered regular checkups. At present, over half of children diagnosed with neuroblastoma and metastases still die of their disease.
Neuroblastoma is the most frequent solid extracerebral tumor in young children. Some 50% of children affected—boys and girls alike—are under two years of age. In France, there are about 150 new cases every year, and one quarter of these are treated at the Institut Curie, a reference center recognized worldwide for its neuroblastoma research and treatment.
Neuroblastoma develops in the sympathetic nervous system, more specifically in the small round cells derived from the neural crest, a transient region characteristic of vertebrate embryos. It principally affects the abdomen, and more rarely the thorax, neck, and lower pelvis.
ALK, a key participant in development of neuroblastoma
At the Institut Curie, Olivier Delattre, Director of Inserm Unit 830 “Genetics and Biology of Cancer”, and his team have just shown that the ALK gene is involved right from the earliest stages of neuroblastoma development.
Through a national collaboration with other centers that treat neuroblastoma, and exemplary exchanges between physicians and researchers at the Institut Curie, Olivier Delattre and his group “genetically” analyzed 592 neuroblastoma samples. They found that in these tumors the ALK gene was frequently altered: either there were excess copies or it contained activating mutations. Now, inhibition of the ALK gene in neuroblastoma cells greatly reduces cell proliferation.
The researchers have also shown that in the familial forms of neuroblastoma, mutations of the ALK gene are transmitted to offspring. ALK thus acquires the status of neuroblastoma predisposition gene. In a study of ten familial forms, an American team confirms this result in the same issue of Nature (Y.P. Mosse, et al. Nature, doi:10.103).This discovery should also lead to an improved clinical management and follow-up of at risk patients within neuroblastoma families with ALK mutations. The tight links between the Inserm U830 and Institut Curie Genetics Department, directed by Prof Dominique Stoppa-Lyonnet, should constitute an asset for these clinical applications;
This study was funded by the Ligue contre le cancer, the Association des Parents et des Amis des Enfants Soignés à l’Institut Curie (APAESIC), Bagouz à Manon, Association Hubert Gouin, and Les Amis de Claire et Enfants et Santé.
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