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TRPS1 gene alterations in human subependymoma

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Abstract

Subependymoma is a rare primary brain tumor, constituting 0.07–0.51% of brain tumors. Genetic alterations in subependymoma are largely unknown, but familial occurrences have been reported. Trichorhinophalangeal syndrome type 1 (TRPS1) is a rare hereditary malformation complex caused by mutations in a gene identified in the year 2000 on 8q24.12. We report two patients with TRPS I and surgically treated subependymomas, one of whom has a first degree relative, now deceased, who was affected and also had a subependymoma. We therefore sought a role for the TRPS1 gene in the molecular oncogenesis of subependymoma. Formalin fixed tumor specimens and saliva samples were obtained from the two index patients as well as tumor samples from six sporadic subependymoma surgical specimens. A heterozygous TRPS1 germ line mutation predicted to cause a frame shift leading to a premature stop codon was found in the first index patient and also present in the associated tumor. No germline mutation was found in the second index patient, but his tumor displayed copy number neutral loss of heterozygosity in TRPS1. TRPS1 mutation analysis of the sporadic subependymomas revealed genetic, mostly loss of function alterations in one-third (two of six) of samples. Genetic alterations in TRPS1 likely play a role in at least a subgroup of subependymomas. Confirmation and further (epi)genetic investigations, ideally in newly acquired, fresh-frozen tumor samples, are warranted.

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Authors and Affiliations

  1. Human Genomics Research Group, Department of Biomedicine, University Hospital Basel, Basel, Switzerland

    Sascha B. Fischer, Michelle Attenhofer & Karl Heinimann

  2. Medical Genetics, University Hospital Basel, Basel, Switzerland

    Sascha B. Fischer, Michelle Attenhofer & Karl Heinimann

  3. Department of Pathology, Oregon Health & Science University, Portland, OR, USA

    Sakir H. Gultekin

  4. Department of Neurological Surgery, Oregon Health & Science University, 3303 SW Bond Ave., Mail Code: CH8N, Portland, OR, 97239, USA

    Donald A. Ross

  5. Operative Care Division, Portland Veterans Administration Medical Center, Portland, OR, USA

    Donald A. Ross

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  1. Sascha B. Fischer
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  2. Michelle Attenhofer
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Correspondence to Donald A. Ross.

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All procedures performed in the present study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Karl Heinimann and Donald A. Ross are equal contributing senior authors.

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Fischer, S.B., Attenhofer, M., Gultekin, S.H. et al. TRPS1 gene alterations in human subependymoma. J Neurooncol 134, 133–138 (2017). https://doi.org/10.1007/s11060-017-2496-7

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  • DOI: https://doi.org/10.1007/s11060-017-2496-7

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