title: Somatic alterations of the SMAD-2 gene in human colorectal cancers.
abstract: The SMAD-2 gene, which is located at 18q21, has been identified as a candidate tumour-suppressor gene from work on colorectal cancers. The aim of the present study was to determine the clinical alterations and the significance of its mutations in a series of colorectal cancers previously examined for SMAD-4/DPC-4 gene. Mutation analyses of the SMAD-2 gene were carried out on cDNA samples from 36 primary colorectal cancer specimens using a combination of the polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP) and DNA sequencing. Only one missense mutation (2.8%), producing an amino acid substitution in the highly conserved region, and two homozygous deletions (5.5%) of the total coding region of the SMAD-2 gene were detected in the 36 cancers. The SMAD-2 gene may play a role as a candidate tumour-suppressor gene in a small fraction of colorectal cancers. However, allelic loss at 18q21 is very often seen in this type of tumour. Even in combination with changes in SMAD-4, the observed frequency was not sufficient to account for all 18q21 deletions in colorectal cancers. Thus, another tumour-suppressor gene, such as DCC, discovered as the first tumour-suppressor candidate in the region may also exist in this chromosome region.
authors.affiliation: Department of Surgery II, Gifu University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Takagi
authors.forename: H
authors.initials: H
authors.lastname: Koumura
authors.forename: M
authors.initials: M
authors.lastname: Futamura
authors.forename: S
authors.initials: S
authors.lastname: Aoki
authors.forename: K
authors.initials: K
authors.lastname: Ymaguchi
authors.forename: H
authors.initials: H
authors.lastname: Kida
authors.forename: H
authors.initials: H
authors.lastname: Tanemura
authors.forename: K
authors.initials: K
authors.lastname: Shimokawa
authors.forename: S
authors.initials: S
authors.lastname: Saji
mesh_terms: D000368:Aged; D002887:Chromosomes, Human, Pair 18; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D018807:Polymorphism, Single-Stranded Conformational; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051899:Smad2 Protein; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D015534:Trans-Activators