A series of papers in the 16 October 2008 issue of Nature reported an association between ALK mutations and neuroblastoma whereby activating mutations were observed in a large majority of familial cases as well as some sporadic ones. On average, around 8% of patients will carry an ALK mutation typically within the kinase domain of the protein and this generally correlates with a poor prognosis. The majority of patients (over 85%) will carry mutations at one of two sites: F1174 or R1275. The location of the mutation can determine the sensitivity of the tumour cells to ALK inhibitors and therefore affect treatment outcome.
Neuroblastoma of the Adrenal Gland (Image courtesy of Ed Uthman)