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 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.
Translational Oncopathology, Department of Pathology, IRCCS A.O.U. San Martino-IST, National Cancer Research Institute, Genoa, Italy.
Simona
S
Coco
Marilena
M
De Mariano
Francesca
F
Valdora
Tiziana
T
Servidei
Vita
V
Ridola
Immacolata
I
Andolfo
André
A
Oberthuer
Gian Paolo
GP
Tonini
Luca
L
Longo
D000293:Adolescent; D000708:Anaplasia / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000077548:Anaplastic Lymphoma Kinase; D002648:Child; D002675:Child, Preschool; D018388:Codon, Terminator; D004252:DNA Mutational Analysis; D055088:Early Detection of Cancer / Q000379:methods; D004789:Enzyme Activation; D005091:Exons; D016368:Frameshift Mutation; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D018095:Germ-Line Mutation; D006801:Humans; D007223:Infant; D008527:Medulloblastoma / Q000201:enzymology / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*
D018388:Codon, Terminator; D012333:RNA, Messenger; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases