Serrated carcinomas form a subclass of colorectal cancer with distinct molecular basis

Päivi Laiho, Antti Kokko, Sakari Vanharanta, Reijo K Salovaara, Heli Sammalkorpi, Heikki J Järvinen, Jukka-Pekka Mecklin, Tuomo J Karttunen, Karoliina Tuppurainen, Veronica Davalos, Simo Schwartz, Diego Arango, Markus J Mäkinen, Lauri A Aaltonen

    Research output: Contribution to journalArticleScientificpeer-review

    Abstract

    Serrated colorectal carcinomas (CRCs) are morphologically different from conventional CRCs and have been proposed to follow a distinct pathway of CRC formation. Despite studies of single molecular events in this tumor type, the diagnosis of serrated CRC relies on morphology and the putative unique biological character of these tumors has not been established. Here we show that the gene expression pro. ling of 37 CRCs separated serrated and conventional CRCs into two distinct branches in unsupervised hierarchical clustering (P-value 7.8 x 10(-7)), and revealed 201 differentially expressed genes representing potential biomarkers for serrated CRC. Immunohistochemistry was utilized to verify the key findings in the 37 CRCs examined by express ion profiling, and a separate validation set of 37 serrated and 86 conventional CRCs was examined to evaluate the candidate biomarkers in an extended sample material. Ephrin receptor B2, hypoxia-inducible factor 1-alpha and patched appeared as proteins important for genesis of serrated CRC. This study establishes serrated CRCs as a biologically distinct subclass of CRC and represents a step forward in the molecular classification of these cancers. The study also provides a platform to understand the molecular basis of serrated CRC and in long term may contribute to the development of specific treatment options for this tumor type.
    Original languageEnglish
    JournalOncogene
    Volume26
    Issue number2
    Pages (from-to)312-320
    Number of pages9
    ISSN0950-9232
    DOIs
    Publication statusPublished - 2007
    MoE publication typeA1 Journal article-refereed

    Fields of Science

    • 311 Basic medicine

    Cite this

    Laiho, Päivi ; Kokko, Antti ; Vanharanta, Sakari ; Salovaara, Reijo K ; Sammalkorpi, Heli ; Järvinen, Heikki J ; Mecklin, Jukka-Pekka ; Karttunen, Tuomo J ; Tuppurainen, Karoliina ; Davalos, Veronica ; Schwartz, Simo ; Arango, Diego ; Mäkinen, Markus J ; Aaltonen, Lauri A. / Serrated carcinomas form a subclass of colorectal cancer with distinct molecular basis. In: Oncogene. 2007 ; Vol. 26, No. 2. pp. 312-320.
    @article{96ea0705fe784a5898bab7c083a9c291,
    title = "Serrated carcinomas form a subclass of colorectal cancer with distinct molecular basis",
    abstract = "Serrated colorectal carcinomas (CRCs) are morphologically different from conventional CRCs and have been proposed to follow a distinct pathway of CRC formation. Despite studies of single molecular events in this tumor type, the diagnosis of serrated CRC relies on morphology and the putative unique biological character of these tumors has not been established. Here we show that the gene expression pro. ling of 37 CRCs separated serrated and conventional CRCs into two distinct branches in unsupervised hierarchical clustering (P-value 7.8 x 10(-7)), and revealed 201 differentially expressed genes representing potential biomarkers for serrated CRC. Immunohistochemistry was utilized to verify the key findings in the 37 CRCs examined by express ion profiling, and a separate validation set of 37 serrated and 86 conventional CRCs was examined to evaluate the candidate biomarkers in an extended sample material. Ephrin receptor B2, hypoxia-inducible factor 1-alpha and patched appeared as proteins important for genesis of serrated CRC. This study establishes serrated CRCs as a biologically distinct subclass of CRC and represents a step forward in the molecular classification of these cancers. The study also provides a platform to understand the molecular basis of serrated CRC and in long term may contribute to the development of specific treatment options for this tumor type.",
    keywords = "311 Basic medicine",
    author = "P{\"a}ivi Laiho and Antti Kokko and Sakari Vanharanta and Salovaara, {Reijo K} and Heli Sammalkorpi and J{\"a}rvinen, {Heikki J} and Jukka-Pekka Mecklin and Karttunen, {Tuomo J} and Karoliina Tuppurainen and Veronica Davalos and Simo Schwartz and Diego Arango and M{\"a}kinen, {Markus J} and Aaltonen, {Lauri A}",
    year = "2007",
    doi = "10.1038/sj.onc.1209778",
    language = "English",
    volume = "26",
    pages = "312--320",
    journal = "Oncogene",
    issn = "0950-9232",
    publisher = "Nature Publishing Group",
    number = "2",

    }

    Laiho, P, Kokko, A, Vanharanta, S, Salovaara, RK, Sammalkorpi, H, Järvinen, HJ, Mecklin, J-P, Karttunen, TJ, Tuppurainen, K, Davalos, V, Schwartz, S, Arango, D, Mäkinen, MJ & Aaltonen, LA 2007, 'Serrated carcinomas form a subclass of colorectal cancer with distinct molecular basis', Oncogene, vol. 26, no. 2, pp. 312-320. https://doi.org/10.1038/sj.onc.1209778

    Serrated carcinomas form a subclass of colorectal cancer with distinct molecular basis. / Laiho, Päivi; Kokko, Antti; Vanharanta, Sakari; Salovaara, Reijo K; Sammalkorpi, Heli; Järvinen, Heikki J; Mecklin, Jukka-Pekka; Karttunen, Tuomo J; Tuppurainen, Karoliina; Davalos, Veronica; Schwartz, Simo; Arango, Diego; Mäkinen, Markus J; Aaltonen, Lauri A.

    In: Oncogene, Vol. 26, No. 2, 2007, p. 312-320.

    Research output: Contribution to journalArticleScientificpeer-review

    TY - JOUR

    T1 - Serrated carcinomas form a subclass of colorectal cancer with distinct molecular basis

    AU - Laiho, Päivi

    AU - Kokko, Antti

    AU - Vanharanta, Sakari

    AU - Salovaara, Reijo K

    AU - Sammalkorpi, Heli

    AU - Järvinen, Heikki J

    AU - Mecklin, Jukka-Pekka

    AU - Karttunen, Tuomo J

    AU - Tuppurainen, Karoliina

    AU - Davalos, Veronica

    AU - Schwartz, Simo

    AU - Arango, Diego

    AU - Mäkinen, Markus J

    AU - Aaltonen, Lauri A

    PY - 2007

    Y1 - 2007

    N2 - Serrated colorectal carcinomas (CRCs) are morphologically different from conventional CRCs and have been proposed to follow a distinct pathway of CRC formation. Despite studies of single molecular events in this tumor type, the diagnosis of serrated CRC relies on morphology and the putative unique biological character of these tumors has not been established. Here we show that the gene expression pro. ling of 37 CRCs separated serrated and conventional CRCs into two distinct branches in unsupervised hierarchical clustering (P-value 7.8 x 10(-7)), and revealed 201 differentially expressed genes representing potential biomarkers for serrated CRC. Immunohistochemistry was utilized to verify the key findings in the 37 CRCs examined by express ion profiling, and a separate validation set of 37 serrated and 86 conventional CRCs was examined to evaluate the candidate biomarkers in an extended sample material. Ephrin receptor B2, hypoxia-inducible factor 1-alpha and patched appeared as proteins important for genesis of serrated CRC. This study establishes serrated CRCs as a biologically distinct subclass of CRC and represents a step forward in the molecular classification of these cancers. The study also provides a platform to understand the molecular basis of serrated CRC and in long term may contribute to the development of specific treatment options for this tumor type.

    AB - Serrated colorectal carcinomas (CRCs) are morphologically different from conventional CRCs and have been proposed to follow a distinct pathway of CRC formation. Despite studies of single molecular events in this tumor type, the diagnosis of serrated CRC relies on morphology and the putative unique biological character of these tumors has not been established. Here we show that the gene expression pro. ling of 37 CRCs separated serrated and conventional CRCs into two distinct branches in unsupervised hierarchical clustering (P-value 7.8 x 10(-7)), and revealed 201 differentially expressed genes representing potential biomarkers for serrated CRC. Immunohistochemistry was utilized to verify the key findings in the 37 CRCs examined by express ion profiling, and a separate validation set of 37 serrated and 86 conventional CRCs was examined to evaluate the candidate biomarkers in an extended sample material. Ephrin receptor B2, hypoxia-inducible factor 1-alpha and patched appeared as proteins important for genesis of serrated CRC. This study establishes serrated CRCs as a biologically distinct subclass of CRC and represents a step forward in the molecular classification of these cancers. The study also provides a platform to understand the molecular basis of serrated CRC and in long term may contribute to the development of specific treatment options for this tumor type.

    KW - 311 Basic medicine

    U2 - 10.1038/sj.onc.1209778

    DO - 10.1038/sj.onc.1209778

    M3 - Article

    VL - 26

    SP - 312

    EP - 320

    JO - Oncogene

    JF - Oncogene

    SN - 0950-9232

    IS - 2

    ER -