RET and NTRK1 proto-oncogenes in human diseases

Authors

  • Luisella Alberti,

    1. Operative Unit “Molecular Mechanisms of Tumor Growth and Progression,” Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy
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  • Cristiana Carniti,

    1. Operative Unit “Molecular Mechanisms of Tumor Growth and Progression,” Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy
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  • Claudia Miranda,

    1. Operative Unit “Molecular Mechanisms of Tumor Growth and Progression,” Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy
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  • Emanuela Roccato,

    1. Operative Unit “Molecular Mechanisms of Tumor Growth and Progression,” Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy
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  • Marco A. Pierotti

    Corresponding author
    1. Operative Unit “Molecular Mechanisms of Tumor Growth and Progression,” Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy
    • Department of Experimental Oncology—Istituto Nazionale Tumori, Via G. Venezian, 1 20133, Milan, Italy.
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  • The authors have contributed equally to this work; specifically Luisella Alberti and Cristiana Carniti for RET and Claudia Miranda and Emanuela Roccato for NTRK1 analysis.

Abstract

RET and NTRK1 are receptor tyrosine kinase (RTK) proteins which play a role in the development and maturation of specific component of the nervous system. Their alterations have been associated to several human diseases, including some forms of cancer and developmental abnormalities. These features have contributed to the concept that one gene can be responsible for more than one disease. Moreover, both genes encoding for the two RTKs show genetic alterations that belong to either “gain of function” or “loss of function” class of mutations. In fact, receptor rearrangements or point mutations convert RET and NTRK1 in dominantly acting transforming genes leading to thyroid tumors, whereas inactivating mutations, associated with Hirschsprung's disease (HSCR) and congenital insensitivity to pain with anhidrosis (CIPA), impair RET and NTRK1 functions, respectively. In this review we have summarized the main features of the two receptors, their physiological and pathological roles. In addition, we attempted to identify the correlations between the different genetic alterations and the related pathogenetic mechanisms. © 2003 Wiley-Liss, Inc.

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