Clinical feature of anaplastic lymphoma kinase-mutated neuroblastoma.
OBJECTIVE
Anaplastic lymphoma kinase (ALK) has recently been identified as a gene conferring a predisposition for neuroblastoma. We have analyzed tyrosine kinase domain mutations and amplification/expression of the ALK gene and focused on clinical features of neuroblastoma cases with ALK aberrations.


METHODS
The frequency of ALK mutations, copy number gain, and expression were analyzed in 538 neuroblastoma tumors derived from 361 cases, including 161 cases detected by mass screening. These cases were analyzed according to clinicopathologic features including the International Neuroblastoma Staging System and patient outcomes.


RESULTS
Three cases (0.8%) had ALK amplification, and 16 cases (5.2%) had missense mutations at positions F1174, F1245, D1249, and R1275. Among them, 7 cases were diagnosed at more than 14 months of age, and 11 cases were infants, including 9 cases detected by mass screening and 1 multiple neuroblastoma with a germline mutation. Of the 11 infants, 3 cases relapsed, and 1 case died of disease. Among cases detected by screening, activated ALK cases showed significantly worse prognosis (P = .002). Of 7 older cases, 5 had MYC amplifications, and 5 died of disease. The expression levels of ALK were up-regulated in cases with unfavorable outcomes. In cases with activated ALK neuroblastoma, survival rates of patients detected by screening were significantly better than those in the clinically detected group (P = .025).


CONCLUSIONS
The results of the present study support the hypothesis that activated ALK tumors represent a specific subset of neuroblastomas. These tumors usually develop in infants and may have a high capacity for recurrence.
Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
Taemi
T
Ogura
Eiso
E
Hiyama
Naomi
N
Kamei
Arata
A
Kamimatsuse
Yuka
Y
Ueda
Kaoru
K
Ogura
D000077548:Anaplastic Lymphoma Kinase; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D009447:Neuroblastoma / Q000175:diagnosis* / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*
C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases