Lüchtenborg Margreet, Weijenberg Matty P, Wark Petra A, Saritas A Merdan, Roemen Guido M J M, van Muijen Goos N P, de Bruïne Adriaan P, van den Brandt Piet A, de Goeij Anton F P M
Nutrition and Toxicology Research Institute Maastricht, Department of Epidemiology, Maastricht University, Maastricht, The Netherlands.
BMC Cancer. 2005 Dec 15;5:160. doi: 10.1186/1471-2407-5-160.
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.
大多数结直肠肿瘤的早期至中期阶段被认为是由Wnt（APC、CTNNB1）和Ras（K-ras）通路的畸变驱动的。一小部分癌症表现出错配修复缺陷。本研究的目的是分析这些基因改变与肿瘤及患者特征的共同出现情况。
在一组656例未经选择的散发性结直肠癌患者中，研究了APC、K-ras、CTNNB1基因的畸变以及hMLH1的表达。此外，根据分子特征将肿瘤分组，并就患者诊断时的年龄、性别、结直肠癌家族史、肿瘤亚定位、Dukes分期和分化程度进行比较。
仅在5/464例患者的肿瘤中观察到CTNNB1基因磷酸化位点（密码子31、33、37和45）的突变。具有截短型APC突变和密码子12和13处激活型K-ras突变的肿瘤出现频率相似（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hMLH1表达。与具有APC和/或K-ras突变的肿瘤患者相比，hMLH1表达缺失的肿瘤患者年龄更大，女性更多见，近端结肠肿瘤更常见，且分化较差。
CTNNB1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在肿瘤和患者特征方面存在主要差异。
