Gene expression signatures for colorectal cancer microsatellite status and HNPCC

Mogens Kruhøffer, J. L Jensen, Päivi Laiho, L Dyrskjot, Reijo Salovaara, Diego Arango, Karin Birkenkamp-Demtröder, Flemming B Sørensen, Lise Lotte Christensen, L Buhl, Jukka-Pekka Mecklin, Heikki J Järvinen, T Thykjaer, Friedrik Wikman, F Bech-Knudsen, M Juhola, Nina Nupponen, Søren Laurberg, Claus Lindbjerg Andersen, Lauri A Aaltonen & 1 others Torben F Ørntoft

    Research output: Contribution to journalArticleScientificpeer-review

    Abstract

    The majority of microsatellite instable (MSI) colorectal cancers are sporadic, but a subset belongs to the syndrome hereditary nonpolyposis colorectal cancer (HNPCC). Microsatellite instability is caused by dysfunction of the mismatch repair (MMR) system that leads to a mutator phenotype, and MSI is correlated to prognosis and response to chemotherapy. Gene expression signatures as predictive markers are being developed for many cancers, and the identification of a signature for MMR deficiency would be of interest both clinically and biologically. To address this issue, we profiled the gene expression of 101 stage II and III colorectal cancers ( 34 MSI, 67 microsatellite stable (MSS)) using high-density oligonucleotide microarrays. From these data, we constructed a nine-gene signature capable of separating the mismatch repair proficient and deficient tumours. Subsequently, we demonstrated the robustness of the signature by transferring it to a real-time RT-PCR platform. Using this platform, the signature was validated on an independent test set consisting of 47 tumours ( 10 MSI, 37 MSS), of which 45 were correctly classified. In a second step, we constructed a signature capable of separating MMR-deficient tumours into sporadic MSI and HNPCC cases, and validated this by a mathematical cross-validation approach. The demonstration that this two-step classification approach can identify MSI as well as HNPCC cases merits further gene expression studies to identify prognostic signatures.
    Original languageEnglish
    JournalBritish Journal of Cancer
    Volume92
    Issue number12
    Pages (from-to)2240-2248
    Number of pages9
    ISSN0007-0920
    DOIs
    Publication statusPublished - 2005
    MoE publication typeA1 Journal article-refereed

    Fields of Science

    • 311 Basic medicine

    Cite this

    Kruhøffer, M., Jensen, J. L., Laiho, P., Dyrskjot, L., Salovaara, R., Arango, D., ... Ørntoft, T. F. (2005). Gene expression signatures for colorectal cancer microsatellite status and HNPCC. British Journal of Cancer, 92(12), 2240-2248. https://doi.org/10.1038/sj.bjc.6602621
    Kruhøffer, Mogens ; Jensen, J. L ; Laiho, Päivi ; Dyrskjot, L ; Salovaara, Reijo ; Arango, Diego ; Birkenkamp-Demtröder, Karin ; Sørensen, Flemming B ; Christensen, Lise Lotte ; Buhl, L ; Mecklin, Jukka-Pekka ; Järvinen, Heikki J ; Thykjaer, T ; Wikman, Friedrik ; Bech-Knudsen, F ; Juhola, M ; Nupponen, Nina ; Laurberg, Søren ; Andersen, Claus Lindbjerg ; Aaltonen, Lauri A ; Ørntoft, Torben F. / Gene expression signatures for colorectal cancer microsatellite status and HNPCC. In: British Journal of Cancer. 2005 ; Vol. 92, No. 12. pp. 2240-2248.
    @article{c7e1cd4268134d75a826a5b42fdec251,
    title = "Gene expression signatures for colorectal cancer microsatellite status and HNPCC",
    abstract = "The majority of microsatellite instable (MSI) colorectal cancers are sporadic, but a subset belongs to the syndrome hereditary nonpolyposis colorectal cancer (HNPCC). Microsatellite instability is caused by dysfunction of the mismatch repair (MMR) system that leads to a mutator phenotype, and MSI is correlated to prognosis and response to chemotherapy. Gene expression signatures as predictive markers are being developed for many cancers, and the identification of a signature for MMR deficiency would be of interest both clinically and biologically. To address this issue, we profiled the gene expression of 101 stage II and III colorectal cancers ( 34 MSI, 67 microsatellite stable (MSS)) using high-density oligonucleotide microarrays. From these data, we constructed a nine-gene signature capable of separating the mismatch repair proficient and deficient tumours. Subsequently, we demonstrated the robustness of the signature by transferring it to a real-time RT-PCR platform. Using this platform, the signature was validated on an independent test set consisting of 47 tumours ( 10 MSI, 37 MSS), of which 45 were correctly classified. In a second step, we constructed a signature capable of separating MMR-deficient tumours into sporadic MSI and HNPCC cases, and validated this by a mathematical cross-validation approach. The demonstration that this two-step classification approach can identify MSI as well as HNPCC cases merits further gene expression studies to identify prognostic signatures.",
    keywords = "311 Basic medicine",
    author = "Mogens Kruh{\o}ffer and Jensen, {J. L} and P{\"a}ivi Laiho and L Dyrskjot and Reijo Salovaara and Diego Arango and Karin Birkenkamp-Demtr{\"o}der and S{\o}rensen, {Flemming B} and Christensen, {Lise Lotte} and L Buhl and Jukka-Pekka Mecklin and J{\"a}rvinen, {Heikki J} and T Thykjaer and Friedrik Wikman and F Bech-Knudsen and M Juhola and Nina Nupponen and S{\o}ren Laurberg and Andersen, {Claus Lindbjerg} and Aaltonen, {Lauri A} and {\O}rntoft, {Torben F}",
    year = "2005",
    doi = "10.1038/sj.bjc.6602621",
    language = "English",
    volume = "92",
    pages = "2240--2248",
    journal = "British Journal of Cancer",
    issn = "0007-0920",
    publisher = "Nature Publishing Group",
    number = "12",

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    Kruhøffer, M, Jensen, JL, Laiho, P, Dyrskjot, L, Salovaara, R, Arango, D, Birkenkamp-Demtröder, K, Sørensen, FB, Christensen, LL, Buhl, L, Mecklin, J-P, Järvinen, HJ, Thykjaer, T, Wikman, F, Bech-Knudsen, F, Juhola, M, Nupponen, N, Laurberg, S, Andersen, CL, Aaltonen, LA & Ørntoft, TF 2005, 'Gene expression signatures for colorectal cancer microsatellite status and HNPCC', British Journal of Cancer, vol. 92, no. 12, pp. 2240-2248. https://doi.org/10.1038/sj.bjc.6602621

    Gene expression signatures for colorectal cancer microsatellite status and HNPCC. / Kruhøffer, Mogens; Jensen, J. L; Laiho, Päivi; Dyrskjot, L; Salovaara, Reijo; Arango, Diego; Birkenkamp-Demtröder, Karin; Sørensen, Flemming B; Christensen, Lise Lotte; Buhl, L; Mecklin, Jukka-Pekka; Järvinen, Heikki J; Thykjaer, T; Wikman, Friedrik; Bech-Knudsen, F; Juhola, M; Nupponen, Nina; Laurberg, Søren; Andersen, Claus Lindbjerg; Aaltonen, Lauri A; Ørntoft, Torben F.

    In: British Journal of Cancer, Vol. 92, No. 12, 2005, p. 2240-2248.

    Research output: Contribution to journalArticleScientificpeer-review

    TY - JOUR

    T1 - Gene expression signatures for colorectal cancer microsatellite status and HNPCC

    AU - Kruhøffer, Mogens

    AU - Jensen, J. L

    AU - Laiho, Päivi

    AU - Dyrskjot, L

    AU - Salovaara, Reijo

    AU - Arango, Diego

    AU - Birkenkamp-Demtröder, Karin

    AU - Sørensen, Flemming B

    AU - Christensen, Lise Lotte

    AU - Buhl, L

    AU - Mecklin, Jukka-Pekka

    AU - Järvinen, Heikki J

    AU - Thykjaer, T

    AU - Wikman, Friedrik

    AU - Bech-Knudsen, F

    AU - Juhola, M

    AU - Nupponen, Nina

    AU - Laurberg, Søren

    AU - Andersen, Claus Lindbjerg

    AU - Aaltonen, Lauri A

    AU - Ørntoft, Torben F

    PY - 2005

    Y1 - 2005

    N2 - The majority of microsatellite instable (MSI) colorectal cancers are sporadic, but a subset belongs to the syndrome hereditary nonpolyposis colorectal cancer (HNPCC). Microsatellite instability is caused by dysfunction of the mismatch repair (MMR) system that leads to a mutator phenotype, and MSI is correlated to prognosis and response to chemotherapy. Gene expression signatures as predictive markers are being developed for many cancers, and the identification of a signature for MMR deficiency would be of interest both clinically and biologically. To address this issue, we profiled the gene expression of 101 stage II and III colorectal cancers ( 34 MSI, 67 microsatellite stable (MSS)) using high-density oligonucleotide microarrays. From these data, we constructed a nine-gene signature capable of separating the mismatch repair proficient and deficient tumours. Subsequently, we demonstrated the robustness of the signature by transferring it to a real-time RT-PCR platform. Using this platform, the signature was validated on an independent test set consisting of 47 tumours ( 10 MSI, 37 MSS), of which 45 were correctly classified. In a second step, we constructed a signature capable of separating MMR-deficient tumours into sporadic MSI and HNPCC cases, and validated this by a mathematical cross-validation approach. The demonstration that this two-step classification approach can identify MSI as well as HNPCC cases merits further gene expression studies to identify prognostic signatures.

    AB - The majority of microsatellite instable (MSI) colorectal cancers are sporadic, but a subset belongs to the syndrome hereditary nonpolyposis colorectal cancer (HNPCC). Microsatellite instability is caused by dysfunction of the mismatch repair (MMR) system that leads to a mutator phenotype, and MSI is correlated to prognosis and response to chemotherapy. Gene expression signatures as predictive markers are being developed for many cancers, and the identification of a signature for MMR deficiency would be of interest both clinically and biologically. To address this issue, we profiled the gene expression of 101 stage II and III colorectal cancers ( 34 MSI, 67 microsatellite stable (MSS)) using high-density oligonucleotide microarrays. From these data, we constructed a nine-gene signature capable of separating the mismatch repair proficient and deficient tumours. Subsequently, we demonstrated the robustness of the signature by transferring it to a real-time RT-PCR platform. Using this platform, the signature was validated on an independent test set consisting of 47 tumours ( 10 MSI, 37 MSS), of which 45 were correctly classified. In a second step, we constructed a signature capable of separating MMR-deficient tumours into sporadic MSI and HNPCC cases, and validated this by a mathematical cross-validation approach. The demonstration that this two-step classification approach can identify MSI as well as HNPCC cases merits further gene expression studies to identify prognostic signatures.

    KW - 311 Basic medicine

    U2 - 10.1038/sj.bjc.6602621

    DO - 10.1038/sj.bjc.6602621

    M3 - Article

    VL - 92

    SP - 2240

    EP - 2248

    JO - British Journal of Cancer

    JF - British Journal of Cancer

    SN - 0007-0920

    IS - 12

    ER -

    Kruhøffer M, Jensen JL, Laiho P, Dyrskjot L, Salovaara R, Arango D et al. Gene expression signatures for colorectal cancer microsatellite status and HNPCC. British Journal of Cancer. 2005;92(12):2240-2248. https://doi.org/10.1038/sj.bjc.6602621