Codon 201(Gly) polymorphic type of the DCC gene is related to disseminated neuroblastoma.
The deleted in colorectal carcinoma (DCC) gene is a potential tumor-suppressor gene on chromosome 18q21.3. The relatively high frequency of loss of heterozygosity (LOH) and loss of expression of this gene in neuroblastoma, especially in the advanced stages, imply the possibility of involvement of the DCC gene in progression of neuroblastoma. However, only few typical mutations have been identified in this gene, indicating that other possible mechanisms for the inactivation of this gene may exist. A polymorphic change (Arg to Gly) at DCC codon 201 is related to advanced colorectal carcinoma and increases in the tumors with absent DCC protein expression. In order to understand whether this change is associated with the development or progression of neuroblastoma, we investigated codon 201 polymorphism of the DCC gene in 102 primary neuroblastomas by polymerase chain reaction single-strand conformation polymorphism. We found no missense or nonsense mutations, but a polymorphic change from CGA (Arg) to GGA (Gly) at codon 201 resulting in three types of polymorphism: codon 201(Gly) type, codon 201(Arg/Gly) type, and codon 201(Arg) type. The codon 201(Gly) type occurred more frequently in disseminated (stages IV and IVs) neuroblastomas (72%) than in localized (stages I, II, and III) tumors (48%) (P=.035), and normal controls (38%) (P=.024). In addition, the codon 201(Gly) type was significantly more common in tumors found clinically (65%) than in those found by mass screening (35%) (P=.002). The results suggested that the codon 201(Gly) type of the DCC gene might be associated with a higher risk of disseminating neuroblastoma.
Kong
X T
XT
Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Choi
S H
SH
Bessho
F
F
Kobayashi
M
M
Hanada
R
R
Yamamoto
K
K
Hayashi
Y
Y
D000293:Adolescent; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003062:Codon; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism; D000075389:DCC Receptor; D005091:Exons / Q000235:genetics; D005260:Female; D016163:Genes, DCC / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan / Q000453:epidemiology; D008297:Male; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D011956:Receptors, Cell Surface; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
D015815:Cell Adhesion Molecules; D003062:Codon; D000075389:DCC Receptor; C501909:DCC protein, human; D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins