Expression of neuronal src mRNA as a favorable marker and inverse correlation to N-myc gene amplification in human neuroblastomas.
Neuron-specific src mRNA, which is expressed in human brain tissue by alternative splicing, is associated with neural differentiation. Neuronal c-srcNI expression may be associated with the ability of neuroblastomas to mature; furthermore, c-srcN2 mRNA is induced in chemically differentiated neuroblastoma cells in vitro. The prognosis of a patient with a neuroblastoma is strongly affected by the ability of the tumor to differentiate in vivo. In order to clarify the relationship between neuronal src mRNA expression and the clinical outcome of a neuroblastoma, we analyzed the expression of src mRNA in neuroblastoma tissues from 28 patients by SI-nuclease-protection assay. N-myc gene amplification was also examined by Southern blot hybridization. The clinical significance of neuronal src mRNA expression and its relevance to N-myc gene amplification was also investigated. A high ratio (more than 10%) of c-srcN2 mRNA expression was observed in all early-stage tumors and in advanced neuroblastomas with a favorable prognosis. In contrast, in advanced neuroblastomas with an aggressive clinical phenotype, c-srcN2 mRNA expression was found at a low ratio (below 10%). Genomic amplification of the N-myc gene and expression of c-srcN2 mRNAs were inversely correlated. When combined with other prognostic markers such as N-myc gene amplification, the expression of c-srcN2 mRNA may be a new biological marker to predict the prognosis of patients with neuroblastomas.
Matsunaga
T
T
Department of Pediatric Surgery, Chiba University, School of Medicine, Japan.
Shirasawa
H
H
Tanabe
M
M
Ohnuma
N
N
Kawamura
K
K
Etoh
T
T
Takahashi
H
H
Simizu
B
B
D015139:Blotting, Southern; D000081247:CSK Tyrosine-Protein Kinase; D002675:Child, Preschool; D005260:Female; D005784:Gene Amplification; D015870:Gene Expression; D016259:Genes, myc; D006238:Haploidy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000502:physiology*; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics; D012326:RNA Splicing; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D015719:Single-Strand Specific DNA and RNA Endonucleases; D019061:src-Family Kinases
D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D016392:Proto-Oncogene Proteins pp60(c-src); D019061:src-Family Kinases; C000631346:CSK protein, human; D015719:Single-Strand Specific DNA and RNA Endonucleases