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The molecular aspects of chordoma

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Abstract

Chordomas are one of the rarest bone tumors, and they originate from remnants of embryonic notochord along the spine, more frequently at the skull base and sacrum. Although they are relatively slow growing and low grade, chordomas are highly recurrent, aggressive, locally invasive, and prone to metastasize to the lungs, bone, and the liver. Chordomas highly and generally show a dual epithelial-mesenchymal differentiation. These tumors resist chemotherapy and radiotherapy; therefore, radical surgery and high-dose radiation are the most used treatments, although there is no standard way to treat the disease. The molecular biology process behind the initiation and progression of a chordoma needs to be revealed for a better understanding of the disease and to develop more effective therapies. Efforts to discover the mysteries of these molecular aspects have delineated several molecular and genetic alterations in this tumor. Here, we review and describe the emerging insights into the molecular landscape of chordomas.

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Acknowledgments

The authors thank Julie Yamamoto for her editorial assistance.

Conflict of interest

The authors declare no competing financial interests.

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Authors and Affiliations

  1. Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, Istanbul, Turkey

    Sukru Gulluoglu & Ozlem Turksoy

  2. Department of Medical Genetics, Yeditepe University Medical School and Yeditepe University Hospital, Istanbul, Turkey

    Sukru Gulluoglu, Aysegul Kuskucu & Omer Faruk Bayrak

  3. Department of Neurosurgery, Yeditepe University Medical School and Yeditepe University Hospital, Istanbul, Turkey

    Ugur Ture

Authors
  1. Sukru Gulluoglu
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  2. Ozlem Turksoy
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  3. Aysegul Kuskucu
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Correspondence to Omer Faruk Bayrak.

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Comments

Reza Akhavan-Sigari, Göttingen, Germany

This is a review article dealing with genetic and molecular aspects of chordoma. Due to their location, it is difficult to obtain wide-margin resection. The rarity of chordoma and the lack of sufficient in vitro and in vivo models emphasize the difficulty in understanding it and developing effective therapies.

Systemic treatments of chordoma are largely ineffective and new therapeutic approaches are therefore needed. Given the complexity involved, the author has produced a number of positive and welcome outcomes including the literature review, which offers a useful overview of current research and policy, and the resulting bibliography, which provides a very useful resource for current practitioners.

The identification of common molecular patterns in chordomas is crucial to determine those genes most differentially expressed in chordoma and thus to establish which had the most promise for translation into clinically useful targets. To date, no targeted therapeutic strategies have been established for chordomas. Recently, however, a phase II study showed a modest antitumor activity of lapatinib in chordoma.

Amir R. Dehdashti, New York, USA

The authors have made a significant effort to elucidate the pathogenesis, molecular biology, genetics, and potential molecular target for consideration of future treatment in human chordomas. Although this is a review with no novel information, the summarized data is helpful to skull base neurosurgeons and all those who are involved with these difficult-to-treat lesions. Among all the different pathways and expression profiles involved in chordomas, it seems that brachyury and cytokeratin are more important to focus on as they are not involved in chondrosarcomas and they may contribute to the more aggressive feature of chordomas. Future directions should be probably more focused on those expression profiles. The most important question remains in the explanation for chemoresistance in chordomas. The presence of cancer stem cells in these tumors might be the answer. Working on the latter might help in identifying molecular targets for potential future chemotherapeutic agents. The authors should be commended for this thorough review.

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Gulluoglu, S., Turksoy, O., Kuskucu, A. et al. The molecular aspects of chordoma. Neurosurg Rev 39, 185–196 (2016). https://doi.org/10.1007/s10143-015-0663-x

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  • DOI: https://doi.org/10.1007/s10143-015-0663-x

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