Microsatellite instability in aberrant crypt foci from human colons

Area of Science:

• Gastroenterology
• Oncology
• Molecular Biology

Background:

• Aberrant crypt foci (ACF) are recognized as the earliest microscopic precursors of colon cancer.
• Genes frequently altered early in colorectal tumorigenesis include APC, K-Ras, and DNA mismatch repair (MMR) genes.
• Microsatellite instability (MSI), a hallmark of some MMR-deficient colon cancers, indicates genomic instability.

Purpose of the Study:

• To investigate the presence of microsatellite instability (MSI) in aberrant crypt foci (ACF).
• To determine if MSI occurs early in the development of colon cancer, potentially within ACF.
• To assess the role of DNA mismatch repair gene mutations in early colorectal tumorigenesis.

Main Methods:

• Analysis of 19 ACF samples (> or = 20 crypts/focus) and adjacent normal colonic mucosa from 10 colon cancer patients.
• DNA extraction from ACF and normal mucosa specimens.
• Microsatellite instability analysis using molecular techniques.

Main Results:

• Microsatellite instability (MSI) was detected in DNA from two ACF samples obtained from two different patients.
• No MSI was observed in any of the DNA samples from the microscopically normal colonic mucosa.
• These findings indicate MSI is present in early precursor lesions.

Conclusions:

• Aberrant crypt foci (ACF) play a significant role as precursors in colon cancer development.
• The presence of MSI in ACF provides evidence that DNA mismatch repair gene alterations are early somatic events in colon cancer.
• This study supports the hypothesis that ACF are critical early lesions in the progression to colorectal cancer.