Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands Cohort Study.
Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands Cohort Study.
复制标题
荷兰队列研究中散发性结直肠癌中 APC、CTNNB1 和 K-ras 基因的突变以及 hMLH1 的表达。
DOI：
10.1186/1471-2407-5-160
复制
发表时间：
2005-12-15
期刊：
影响因子：
3.8
通讯作者：
de Goeij AF
中科院分区：
文献类型：
--
作者：
Lüchtenborg M;Weijenberg MP;Wark PA;Saritas AM;Roemen GM;van Muijen GN;de Bruïne AP;van den Brandt PA;de Goeij AF
大多数结直肠肿瘤的早期至中期被认为是由Wnt（APC，CTNNB 1）和Ras（K-ras）通路中的畸变驱动的。较小比例的癌症表现出错配修复缺陷。本研究的目的是分析这些遗传变异与肿瘤和患者特征的共同发生。在一组656例散发性结直肠癌患者中，研究了APC、K-ras、CTNNB 1基因的畸变和hMLH 1的表达。此外，根据分子特征将肿瘤分组，并比较患者诊断时的年龄、性别、结直肠癌家族史、肿瘤亚定位、Dukes分期和分化。CTNNB 1基因磷酸化位点（密码子31、33、37和45）的突变仅在5/464例患者的肿瘤中观察到。在密码子12和13中具有截短APC突变和激活K-ras突变的肿瘤以相似的频率发生（分别为37%（245/656）和36%（235/656））。17%的肿瘤同时存在APC和K-ras突变（109/656）。所有肿瘤中有9%（58/656）缺乏hMLH 1表达。hMLH 1表达缺失的肿瘤患者年龄较大，更常见于女性，与APC和/或K-ras突变的肿瘤患者相比，近端结肠肿瘤的分化较差。CTNNB 1突变在散发性结直肠癌中似乎不太重要。基于错配修复缺陷的患者组之间发现肿瘤和患者特征的主要差异。
The early to intermediate stages of the majority of colorectal tumours are thought to be driven by aberrations in the Wnt (APC, CTNNB1) and Ras (K-ras) pathways. A smaller proportion of cancers shows mismatch repair deficiency. The aim of this study was to analyse the co-occurrence of these genetic alterations in relation to tumour and patient characteristics. In a group of 656 unselected sporadic colorectal cancer patients, aberrations in the APC, K-ras, CTNNB1 genes, and expression of hMLH1 were investigated. Additionally, tumours were divided in groups based on molecular features and compared with respect to patient's age at diagnosis, sex, family history of colorectal cancer, tumour sub-localisation, Dukes' stage and differentiation. Mutations at the phosphorylation sites (codons 31, 33, 37, and 45) in the CTNNB1 gene were observed in tumours from only 5/464 patients. Tumours with truncating APC mutations and activating K-ras mutations in codons 12 and 13 occurred at similar frequencies (37% (245/656) and 36% (235/656), respectively). Seventeen percent of tumours harboured both an APC and a K-ras mutation (109/656). Nine percent of all tumours (58/656) lacked hMLH1 expression. Patients harbouring a tumour with absent hMLH1 expression were older, more often women, more often had proximal colon tumours that showed poorer differentiation when compared to patients harbouring tumours with an APC and/or K-ras mutation. CTNNB1 mutations seem to be of minor importance in sporadic colorectal cancer. The main differences in tumour and patient characteristics are found between groups of patients based on mismatch repair deficiency.
登录
查看更多内容
影响因子：
8.8
作者：
Breivik, J;Meling, G I;Spurkland, A;Rognum, T O;Gaudernack, G
通讯作者：
Gaudernack, G
影响因子：
10.4
作者：
CAPELLA, G;CRONAUERMITRA, S;PERUCHO, M
通讯作者：
PERUCHO, M
影响因子：
8.4
作者：
Kressner, U;Bjorheim, J;Borresen-Dale, AL
通讯作者：
Borresen-Dale, AL
影响因子：
29.4
作者：
Konishi, M;KikuchiYanoshita, R;Miyaki, M
通讯作者：
Miyaki, M
影响因子：
158.5
作者：
Aaltonen, LA;Salovaara, R;ValKamo, E
通讯作者：
ValKamo, E