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K-ras mutations in putative preneoplastic lesions in human colon
T P Pretlow1, T A Brasitus, N C Fulton
1Institute of Pathology, Case Western Reserve University, Cleveland, Ohio.
Journal of the National Cancer Institute
|December 15, 1993
Summary
Mutations in K-ras are frequently found in aberrant crypt foci, which are early pre-cancerous lesions in the human colon. This discovery suggests K-ras mutation is an initial genetic event in colon cancer development, often preceding polyp formation.
Area of Science:
- Oncology
- Gastroenterology
- Molecular Biology
Background:
- K-ras (KRAS2) mutations are implicated in human colon cancer development.
- Aberrant crypt foci (ACF) are microscopic pre-neoplastic lesions found in the colon.
- ACF occur frequently in carcinogen-treated animals and in patients with colon cancer.
Purpose of the Study:
- To investigate K-ras mutational activation in human colon aberrant crypt foci.
- To determine if K-ras mutations are an early event in colon tumorigenesis.
Main Methods:
- Microdissection of ACF and normal crypts from human colonic mucosa.
- Polymerase chain reaction (PCR) amplification of the K-ras codon 12 region.
- Dot-blot hybridization using specific oligonucleotide probes to detect mutations.
Main Results:
- K-ras mutations were detected in 73% (11 of 15) of aberrant crypt foci.
- No K-ras mutations were found in 27 morphologically normal crypt areas from the same patients.
Conclusions:
- K-ras mutation is the earliest identified genetic event in human colon tumorigenesis.
- Aberrant crypt foci are likely precursors to human colon cancer, with K-ras mutation occurring before polyp development.
- Further study of ACF may reveal additional early genetic events in colon cancer.