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Mutated SON putatively causes a cancer syndrome comprising high-risk medulloblastoma combined with café-au-lait spots

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Abstract

Medulloblastoma is the most frequent malignant brain tumor in childhood. This highly malignant neoplasm occurs usually before 10 years of age and more frequently in boys. The 5-year event-free survival rate for high-risk medulloblastoma is low at 62% despite a multimodal therapy including surgical resection, radiation therapy and chemotherapy. We report the case of a boy, who was born to consanguineous parents. Prominently, he had multiple café-au-lait spots. At the age of 3 years he was diagnosed with a high-risk metastatic medulloblastoma. The patient died only 11 months after diagnosis of a fulminant relapse presenting as meningeal and spinal dissemination. Whole-exome sequencing of germline DNA was employed to detect the underlying mutation for this putative cancer syndrome presenting with the combination of medulloblastoma and skin alterations. After screening all possible homozygous gene SNVs, we identified a mutation of SON, an essential protein in cell cycle regulation and cell proliferation, as the most likely genetic cause.

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Acknowledgements

The authors thank Michael Gombert for sequencing.

Funding

Celine Chiu was funded by the Düsseldorf School of Oncology (funded by the Comprehensive Cancer Center Düsseldorf/Deutsche Krebshilfe and the Medical Faculty HHU Düsseldorf) and Jessica I. Hoell by Deutsche Forschungsgemeinschaft (DFG, HO 5456/3-1).

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Authors and Affiliations

  1. Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, University Children’s Hospital, Heinrich-Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany

    Celine Chiu, Stefanie Loth, Michaela Kuhlen, Sebastian Ginzel, Arndt Borkhardt & Jessica I. Hoell

  2. Department of Diagnostic and Interventional Radiology, Medical Faculty, University of Duesseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany

    Jörg Schaper

  3. Department of Pediatrics, Sana Kliniken Duisburg, Zu den Rehwiesen 9, 47055, Duisburg, Germany

    Thorsten Rosenbaum

  4. Institute of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn, DZNE German Center for Neurodegenerative Diseases, Sigmund-Freud-Str. 25, 53127, Bonn, Germany

    Torsten Pietsch

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  1. Celine Chiu
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  2. Stefanie Loth
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  3. Michaela Kuhlen
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  4. Sebastian Ginzel
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  7. Torsten Pietsch
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  8. Arndt Borkhardt
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  9. Jessica I. Hoell
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Correspondence to Jessica I. Hoell.

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Chiu, C., Loth, S., Kuhlen, M. et al. Mutated SON putatively causes a cancer syndrome comprising high-risk medulloblastoma combined with café-au-lait spots. Familial Cancer 18, 353–358 (2019). https://doi.org/10.1007/s10689-019-00121-z

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