Activation of c-K-ras mutations in human gastrointestinal tumors.
OBJECTIVE
Ras genes are the most frequently detected oncogenes in human malignancies. Data regarding the frequency of c-K-ras mutations in esophageal, gastric, and small bowel tumors are limited and controversial.


METHODS
DNA was extracted from 262 formalin-fixed, paraffin-embedded sections of gastrointestinal samples and tumors, including Barrett's esophagus, esophageal squamous cell carcinomas and adenocarcinomas, and small and large bowel adenomas and adenocarcinomas. The presence of c-K-ras codon 12 mutations was determined using a nonradioactive polymerase chain reaction-based restriction fragment length polymorphism assay.


RESULTS
c-K-ras mutations were detected in 1 of 39 (2%) patients with Barrett's esophagus, 1 of 21 (5%) adenocarcinomas, 0 of 27 squamous cell carcinomas of the esophagus, and 1 of 32 (3%) gastric adenocarcinomas. It was also present in 8 of 20 (40%) and 10 of 28 (36%) small bowel adenomas and adenocarcinomas, respectively. Similar numbers were observed in 10 of 25 (40%) large bowel adenomas and 11 of 30 adenocarcinomas (37%). Mutations were not associated with age, gender, histology, grade, stage, location, or mortality.


CONCLUSIONS
The frequency of codon 12 c-K-ras mutations in small and large bowel tumors is approximately 10-fold higher than that of tumors in the upper gastrointestinal tract.
Arber
N
N
GI Oncology Unit, Tel-Aviv University, Tel Aviv, Israel. narber@tasmc.health.co.il
Shapira
I
I
Ratan
J
J
Stern
B
B
Hibshoosh
H
H
Moshkowitz
M
M
Gammon
M
M
Fabian
I
I
Halpern
Z
Z
D000230:Adenocarcinoma / Q000235:genetics*; D000236:Adenoma / Q000235:genetics*; D000483:Alleles; D001471:Barrett Esophagus / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D004252:DNA Mutational Analysis; D004938:Esophageal Neoplasms / Q000235:genetics; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics; D007557:Israel; D009519:New York City; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D013274:Stomach Neoplasms / Q000235:genetics