Mutational analysis of beta-catenin and the RAS-RAF signalling pathway in early flat-type colorectal tumours.
Mutational analysis of beta-catenin and the RAS-RAF signalling pathway in early flat-type colorectal tumours.
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DOI：
10.1016/j.ejca.2006.06.029
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发表时间：
2006-11
影响因子：
8.4
通讯作者：
M. Mikami;K. Nosho;Hiroyuki Yamamoto;Taiga Takahashi;T. Maehata;H. Taniguchi;Y. Adachi;A. Imamura;M. Fujita;M. Hosokawa;F. Itoh;K. Imai;Y. Shinomura
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文献类型：
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作者：
M. Mikami;K. Nosho;Hiroyuki Yamamoto;Taiga Takahashi;T. Maehata;H. Taniguchi;Y. Adachi;A. Imamura;M. Fujita;M. Hosokawa;F. Itoh;K. Imai;Y. Shinomura
形态学上，早期大肠肿瘤可分为两类，即弥漫型和扁平型。然而，对后者的遗传机制知之甚少。我们研究了310例早期结直肠肿瘤中β-catenin、KRAS、BRAF和PIK 3CA的突变。β-连环蛋白突变在310例肿瘤中检出率为7.1%。在具有凹陷区域的扁平型肿瘤中检测到β-连环蛋白突变的百分比（4/17，23.5%）显著高于其他肿瘤（18/293，6.1%; p=0.0246）。KRAS、BRAF和PIK 3CA突变分别在310例肿瘤中的21.6%、5.4%和1.0%中检出。在7个肿瘤中检测到β-连环蛋白和KRAS或BRAF的伴随突变。在扁平型肿瘤组织（75/193，38.9%）中检测到至少一种基因突变的百分比显著高于扁平型肿瘤组织（25/117，21.4%; p=0.0014），并且与大小显著相关（p=0.0001）。总之，β-catenin突变似乎在扁平型肿瘤中起重要作用，特别是在凹陷区域的肿瘤中。遗传异常可在大肠肿瘤发生的早期阶段出现和积累，并可能有助于扁平型肿瘤的发展。
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 β-catenin, KRAS, BRAF, and PIK3CA in 310 early colorectal tumours. β-catenin mutation was detected in 7.1% of 310 tumours. β-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 β-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, β-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.