Infrequent K-ras codon 12 mutation in serrated adenomas of human colorectum.
BACKGROUND
Serrated adenoma is a new morphological subtype of colorectal adenoma. The lesion provides a distinct morphological route to carcinoma, but the underlying genetic changes have not yet been investigated.


OBJECTIVE
To determine the frequency of K-ras mutation in serrated adenoma.


METHODS
The frequency of K-ras codon 12 point mutation in 20 serrated adenomas, five atypical hyperplastic polyps, and 58 sporadic polypoid adenomas was investigated by nested polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods.


RESULTS
Although most of the serrated adenomas were large (average size 11.4 mm) and polypoid, K-ras codon 12 point mutation was detected in only one of the 20 (5%), which is a significantly lower frequency than that in sporadic polypoid adenomas (18/60; 30%) (p = 0.017). No mutation was detected in the atypical hyperplastic polyps. Three of 20 (15%) serrated adenomas contained a focus of carcinoma in situ, indicating their malignant potential and the existence of a serrated adenoma-carcinoma sequence, but no mutation was detected in the foci of carcinoma in situ.


CONCLUSIONS
K-ras mutation is uncommon in serrated adenomas, indicating a different spectrum of genetic alterations in these lesions from those in typical polypoid sporadic adenomas. This subtype of colorectal adenoma represents a new genetic pathway in the histogenesis of colorectal carcinoma.
Ajioka
Y
Y
First Department of Pathology, School of Medicine, Niigata University, Japan.
Watanabe
H
H
Jass
J R
JR
Yokota
Y
Y
Kobayashi
M
M
Nishikura
K
K
D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D003062:Codon / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D011905:Genes, ras; D006801:Humans; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
D003062:Codon