Reduced or absent expression and codon 201Gly/Arg polymorphism of DCC gene in rhabdomyosarcoma and Ewing's sarcoma/PNET family.
Genetic alterations occurring in various chromosomes have been described in many human tumors. The DCC gene was originally identified in colorectal cancer and was reported as a tumor suppressor gene that might be related to tumor metastasis. We investigated 10 cell lines and 15 fresh tumors of childhood rhabdomyosarcoma, 7 cell lines of Ewing's sarcoma, and 4 cell lines of primitive neuroectodermal tumor (PNET) for the expression and mutation of DCC gene by RT-PCR analysis and PCR-single stranded conformation polymorphism (SSCP) analysis. Twenty-five pairs of primers were used for PCR-SSCP. Six of ten (60%) cell lines of rhabdomyosarcoma and 3 of 7 (43%) cell lines of Ewing's sarcoma showed reduced or absent expression of DCC gene. There was no mobility shift within 24 exons by SSCP analysis, although 3 types of polymorphism were found at codon 201 in exon 3. Direct sequencing of different bands showed types I, II, and I/II representative of codon 201Gly, codon 201Arg, and codon 201Gly/Arg, respectively. The proportion of type I between fresh rhabdomyosarcoma and normal controls was not significant. Our results suggested that the inactivation of DCC gene may play a role in the pathogenesis of a subset of rhabdomyosarcoma and Ewing's sarcoma.
Choi
S H
SH
Department of Pediatrics, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Kong
X T
XT
Taki
T
T
Tsuchida
Y
Y
Kawaguchi
H
H
Kato
H
H
Hanada
R
R
Look
A T
AT
Hayashi
Y
Y
D000293:Adolescent; D019943:Amino Acid Substitution; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D003062:Codon / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016163:Genes, DCC / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D018242:Neuroectodermal Tumors, Primitive / Q000235:genetics / Q000473:pathology; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012208:Rhabdomyosarcoma / Q000235:genetics / Q000473:pathology; D012512:Sarcoma, Ewing / Q000235:genetics / Q000473:pathology; D014407:Tumor Cells, Cultured
D003062:Codon; D004273:DNA, Neoplasm; D012334:RNA, Neoplasm