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Most hereditary neuroblastomas are related to germline mutations in the anaplastic lymphoma kinase gene, according to a report in the August 24 online issue of Nature.

Most hereditary neuroblastomas are related to germline mutations in the anaplastic lymphoma kinase (ALK) gene, according to a report in the August 24 online issue of Nature.

The results also suggest that activating mutations can be acquired somatically, Dr. John M. Maris, from The University of Pennsylvania School of Medicine in Philadelphia, and colleagues note.

Using a whole-genome scan in neuroblastoma families, the researchers found evidence of signal linkage at chromosome bands 2p23-24. Further analysis of these areas revealed three separate missense mutations in the tyrosine kinase domain of ALK.

Testing in 194 high-risk neuroblastoma samples indicated somatically acquired ALK mutations in 12.4 per cent of samples. Nine of the ten mutations identified were predicted to be cancer drivers.

"Our results demonstrate that heritable mutations of ALK are the main cause of familial neuroblastoma, and that germline or acquired activation of this cell-surface kinase is a tractable therapeutic target for this lethal pediatric malignancy," the researchers conclude.

Nature 2008