Analyses of mutation and loss of heterozygosity of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human gastric cancer.
Mutations in the transforming growth factor beta type II receptor (TGFbetaRII) gene have been detected in several human cancer types exhibiting microsatellite instability. Using intron primers previously reported for examination of the entire coding region of the TGFbetaRII gene, 29 sporadic gastric cancers were screened with non-radioactive single strand conformation polymorphism and subsequent DNA sequencing analysis. Mutations of the TGFbetaRII gene were detected in three out of 29 tumors (10%). Two cases showed deletions in a polyadenine tract in both alleles and was positively associated with replication error. One case had an insertion of GA dinucleotide sequence in one allele. Mutations of the TGFbetaRII gene were restricted to exon 3 and other coding regions were not affected. Loss of heterozygosity was detected by analyzing a polymorphic site in intron 2. Three out of nine (33%) informative cases, which were all of intestinal type and advanced cases, showed loss of heterozygosity but neither TGFbetaRII mutation nor replication error was found in these cases. Immunoreactivity of TGFbetaRII in tumor tissues was reduced to a different extent in the gastric cancer with genetically abnormal transforming growth factor. Although the numbers studied are small, homozygous (A)10 deletion or loss of heterozygosity of TGFbetaRII is involved in tumorigenesis and progression of at least some part of sporadic gastric cancer.
First Department of Pathology, Hamamatsu University School of Medicine, Shizuoka, Japan.
R J
RJ
Guo
Y
Y
Wang
E
E
Kaneko
D Y
DY
Wang
H
H
Arai
H
H
Hanai
S
S
Takenoshita
K
K
Hagiwara
C C
CC
Harris
H
H
Sugimura
D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D009154:Mutation; D011110:Polymorphism, Genetic; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*
D018125:Receptors, Transforming Growth Factor beta