Oncogenic mutations of ALK in neuroblastoma.

Abstract

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.

• Authors: Seishi Ogawa, Junko Takita, Masashi Sanada, Yasuhide Hayashi
• Journal: Cancer science (Cancer Sci) Vol. 102 Issue 2 Pg. 302-8 (Feb 2011) ISSN: 1349-7006 [Electronic] England
• PMID: 21205076 (Publication Type: Journal Article, Review)
• Copyright: © 2011 Japanese Cancer Association.

Chemical References

• ALK protein, human
• Anaplastic Lymphoma Kinase
• Protein-Tyrosine Kinases
• Receptor Protein-Tyrosine Kinases

Topics

• Alleles
• Anaplastic Lymphoma Kinase
• Gene Dosage
• Genetic Predisposition to Disease
• Humans
• Mutation
• Neuroblastoma (enzymology, genetics, therapy)
• Protein-Tyrosine Kinases (chemistry, genetics)
• Receptor Protein-Tyrosine Kinases