Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands cohort study

Margreet Lüchtenborg, Matty P. Weijenberg, Petra A. Wark, A. Merdan Saritas, Guido M J M Roemen, Goos N P van Muijen, Adriaan P. de Bruïne, Piet A. van den Brandt, Anton F P M de Goeij

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    Abstract

    Background: 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. Methods: 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. Results: 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. Conclusions: 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.

    Original languageEnglish
    Article number160
    JournalBMC Cancer
    Volume5
    DOIs
    Publication statusPublished - 15 Dec 2005

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    ras Genes
    Netherlands
    Colorectal Neoplasms
    Cohort Studies
    Gene Expression
    Mutation
    Neoplasms
    Codon
    Colon
    Phosphorylation

    ASJC Scopus subject areas

    • Oncology
    • Genetics
    • Cancer Research

    Cite this

    Lüchtenborg, M., Weijenberg, M. P., Wark, P. A., Saritas, A. M., Roemen, G. M. J. M., van Muijen, G. N. P., ... de Goeij, A. F. P. M. (2005). Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands cohort study. BMC Cancer, 5, [160]. https://doi.org/10.1186/1471-2407-5-160

    Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands cohort study. / 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.

    In: BMC Cancer, Vol. 5, 160, 15.12.2005.

    Research output: Contribution to journalArticle

    Lüchtenborg, M, Weijenberg, MP, Wark, PA, Saritas, AM, Roemen, GMJM, van Muijen, GNP, de Bruïne, AP, van den Brandt, PA & de Goeij, AFPM 2005, 'Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands cohort study' BMC Cancer, vol. 5, 160. https://doi.org/10.1186/1471-2407-5-160
    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. / Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands cohort study. In: BMC Cancer. 2005 ; Vol. 5.
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    title = "Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands cohort study",
    abstract = "Background: 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. Methods: 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. Results: 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. Conclusions: 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.",
    author = "Margreet L{\"u}chtenborg and Weijenberg, {Matty P.} and Wark, {Petra A.} and Saritas, {A. Merdan} and Roemen, {Guido M J M} and {van Muijen}, {Goos N P} and {de Bru{\"i}ne}, {Adriaan P.} and {van den Brandt}, {Piet A.} and {de Goeij}, {Anton F P M}",
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    T1 - Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands cohort study

    AU - Lüchtenborg, Margreet

    AU - Weijenberg, Matty P.

    AU - Wark, Petra A.

    AU - Saritas, A. Merdan

    AU - Roemen, Guido M J M

    AU - van Muijen, Goos N P

    AU - de Bruïne, Adriaan P.

    AU - van den Brandt, Piet A.

    AU - de Goeij, Anton F P M

    PY - 2005/12/15

    Y1 - 2005/12/15

    N2 - Background: 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. Methods: 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. Results: 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. Conclusions: 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.

    AB - Background: 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. Methods: 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. Results: 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. Conclusions: 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.

    U2 - 10.1186/1471-2407-5-160

    DO - 10.1186/1471-2407-5-160

    M3 - Article

    VL - 5

    JO - BMC Cancer

    JF - BMC Cancer

    SN - 1471-2407

    M1 - 160

    ER -