Mutations of the K-ras and p53 genes in gastric adenocarcinomas from a high-incidence region around Florence, Italy.
K-ras and p53 gene mutations in intestinal-type gastric carcinomas from a high-incidence area around Florence, Italy, were studied by single strand conformation polymorphism and DNA sequencing analysis. Single-strand conformation polymorphism analysis of K-ras indicated aberrant bands in 13 of 34 cases. Sequencing revealed point mutations in 7 (including two at a previously unreported site in codon 11), a significantly higher frequency than reported in countries other than Japan. No K-ras mutations were identified in stage III tumors. Single-strand conformation polymorphisms in p53 exons 5-8 occurred in 30 of 34 cases, with mutations identifiable by direct sequencing in 65% of the cases. Of these, 91% were base substitutions, a value similar to that usually reported, but the percentage of G:C to A:T transitions (90% in this study, 89% in all published European cases combined) differed significantly from that in Oriental cases (48%). The percentage of A:T to G:C transitions was greater in Oriental (22%) than European cases (2%), as was also true for transversions (30% in Oriental tumors, 9% in European tumors). The frequency of mutations at CpG sites (14%) varied significantly from the 67% in cases from a neighboring region in Italy. Helicobacter pylori infection was established in 19 cases and was somewhat more common in cases lacking a p53 mutation.
Hongyo
T
T
Laboratory of Comparative Carcinogenesis, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702, USA.
Buzard
G S
GS
Palli
D
D
Weghorst
C M
CM
Amorosi
A
A
Galli
M
M
Caporaso
N E
NE
Fraumeni
J F
JF
Rice
J M
JM
D000230:Adenocarcinoma / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D000483:Alleles; D001483:Base Sequence; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000032:analysis; D005060:Europe; D005091:Exons; D016158:Genes, p53; D011905:Genes, ras; D005843:Geography; D016481:Helicobacter Infections / Q000175:diagnosis / Q000453:epidemiology; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D007564:Japan / Q000453:epidemiology; D008969:Molecular Sequence Data; D009154:Mutation; D009367:Neoplasm Staging; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D013274:Stomach Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis
D017931:DNA Primers; D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53