Identification of ALK germline mutation (3605delG) in pediatric anaplastic medulloblastoma

The anaplastic lymphoma kinase (ALK) gene has been found either rearranged or mutated in several neoplasms such as anaplastic large-cell lymphoma, non-small-cell lung cancer, neuroblastoma and anaplastic thyroid cancer. Medulloblastoma (MB) is an embryonic pediatric cancer arising from nervous syste...

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Bibliographic Details
Published in:	Journal of human genetics 2012-10, Vol.57 (10), p.682-684
Main Authors:	Coco, Simona, De Mariano, Marilena, Valdora, Francesca, Servidei, Tiziana, Ridola, Vita, Andolfo, Immacolata, Oberthuer, André, Tonini, Gian Paolo, Longo, Luca
Format:	Article
Language:	eng
Subjects:	Adolescent ALK protein Anaplasia - enzymology Anaplasia - genetics Anaplasia - pathology Anaplastic large-cell lymphoma Cancer Child Child, Preschool Codon, Terminator DNA Mutational Analysis Early Detection of Cancer - methods Embryogenesis Enzyme Activation Exons Frameshift Mutation Gene deletion Gene Expression Regulation, Developmental Gene Expression Regulation, Neoplastic Germ-Line Mutation Humans Infant Kinases Lymphoma Medulloblastoma Medulloblastoma - enzymology Medulloblastoma - genetics mRNA Mutation Nervous system Neuroblastoma Nonsense mutation Pediatrics Protein-tyrosine kinase Receptor Protein-Tyrosine Kinases - genetics RNA, Messenger - genetics RNA, Messenger - metabolism Signal transduction Small cell lung carcinoma Stop codon Thyroid Thyroid cancer Tumors Tyrosine
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Summary:	The anaplastic lymphoma kinase (ALK) gene has been found either rearranged or mutated in several neoplasms such as anaplastic large-cell lymphoma, non-small-cell lung cancer, neuroblastoma and anaplastic thyroid cancer. Medulloblastoma (MB) is an embryonic pediatric cancer arising from nervous system, a tissue in which ALK is expressed during embryonic development. We performed an ALK mutation screening in 52 MBs and we found a novel heterozygous germline deletion of a single base in exon 23 (3605delG) in a case with marked anaplasia. This G deletion results in a frameshift mutation producing a premature stop codon in exon 25 of ALK tyrosine kinase domain. We also screened three human MB cell lines without finding any mutation of ALK gene. Quantitative expression analysis of 16 out of 52 samples showed overexpression of ALK mRNA in three MBs. In the present study, we report the first mutation of ALK found in MB. Moreover, a deletion of ALK gene producing a stop codon has not been detected in human tumors up to now. Further investigations are now required to elucidate whether the truncated form of ALK may have a role in signal transduction.
ISSN:	1434-5161 1435-232X