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

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