Open AccessOncogenic mutations of ALK in neuroblastoma
Author(s) -
Ogawa Seishi,
Takita Junko,
Sanada Masashi,
Hayashi Yasuhide
Publication year - 2011
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2010.01825.x
Subject(s) - neuroblastoma , anaplastic lymphoma kinase , cancer research , crizotinib , germline , biology , tyrosine kinase , receptor protein tyrosine kinases , lymphoma , receptor tyrosine kinase , alk inhibitor , kinase , signal transduction , medicine , genetics , gene , cell culture , immunology , lung cancer , malignant pleural effusion
Neuroblastoma is one of the most common solid cancers among children. Prognosis of advanced neuroblastoma is still poor despite the recent advances in chemo/radiotherapies. In view of improving the clinical outcome of advanced neuroblastoma, it is important to identify the key molecules responsible for the pathogenesis of neuroblastoma and to develop effective drugs that target these molecules. Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase, initially identified through the analysis of a specific translocation associated with a rare subtype of non‐Hodgkin’s lymphoma. Recently it was demonstrated that ALK is frequently mutated in sporadic cases with advanced neuroblastoma. Moreover, germline mutations of ALK were shown to be responsible for the majority of hereditary neuroblastoma. ALK mutants found in neuroblastoma show constitutive active kinase activity and oncogenic potentials. Inhibition of ALK in neuroblastoma cell lines carrying amplified or mutated ALK alleles results in compromised downstream signaling and cell growth, indicating potential roles of small molecule ALK inhibitors in the therapeutics of neuroblastoma carrying mutated ALK kinases. ( Cancer Sci 2011; 102: 302–308)