Mutational analysis of beta-catenin and the RAS-RAF signalling pathway in early flat-type colorectal tumours.
Morphologically, early colorectal tumours can be divided into two groups, protruded-type and flat-type. However, little is known about genetic mechanisms of the latter. We investigated mutations of beta-catenin, KRAS, BRAF, and PIK3CA in 310 early colorectal tumours. beta-catenin mutation was detected in 7.1% of 310 tumours. beta-catenin mutation was detected in a significantly higher percentage of flat-type tumours with depressed areas (4/17, 23.5%) than in other tumours (18/293, 6.1%; p=0.0246). KRAS, BRAF, and PIK3CA mutations were detected in 21.6%, 5.4%, and 1.0% of 310 tumours, respectively. Concomitant mutations of beta-catenin and KRAS or BRAF were detected in seven tumours. Mutation of at least one gene was detected in a significantly higher percentage of flat-type tumour tissues (75/193, 38.9%) than in protruded-type tumour tissues (25/117, 21.4%; p=0.0014), and it was correlated significantly with size (p=0.0001). In conclusion, beta-catenin mutation seemed to play an important role in flat-type tumours, especially in those with depressed areas. The genetic abnormalities could arise and accumulate in the early stage of colorectal tumourigenesis, and seem to contribute to the development of flat-type tumour.
Mikami
Masashi
M
First Department of Internal Medicine, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8543, Japan.
Nosho
Katsuhiko
K
Yamamoto
Hiroyuki
H
Takahashi
Taiga
T
Maehata
Tadateru
T
Taniguchi
Hiroaki
H
Adachi
Yasushi
Y
Imamura
Akimichi
A
Fujita
Masahiro
M
Hosokawa
Masao
M
Itoh
Fumio
F
Imai
Kohzoh
K
Shinomura
Yasuhisa
Y
D000368:Aged; D000369:Aged, 80 and over; D002450:Cell Communication; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics*
D051176:beta Catenin; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf