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Rapamycin treatment for a child with germline PTEN mutation

Nature Clinical Practice Oncology volume 5, pages 357–361 (2008)Cite this article

Abstract

Background A 9-month-old boy with Proteus syndrome and a de novo germline mutation in the tumor suppressor PTEN was referred to a specialist centre for management. Over the first years of life, the patient developed life-threatening respiratory dysfunction and malnutrition because of progressive growth of hamartomas affecting the chest, mediastinum, abdomen and pelvis.

Investigations Physical examination, CT scans of the mediastinum, pelvis and abdomen, measurement of serum insulin-like growth factor binding protein-2, and investigation of the effect of the PTEN mutation on phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling in an in vitro cell model.

Diagnosis PTEN hamartoma tumor syndrome, specifically Proteus syndrome.

Management Oral rapamycin.

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Figure 1: Response to rapamycin therapy in anterior mediastinal and pelvic masses and mesenteric adenopathy.
Figure 2: IGFBP-2 response to rapamycin.

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Acknowledgements

DJM, TNT and JLM contributed equally to this work. DJM and JLM are Cancer Institute NSW Research Fellows, and WYC is a Cancer Institute NSW Research Scholar. TNT is supported by Fellowships from the National Health and Medical Research Council (Peter Doherty Fellowship) and the Cancer Institute NSW (Clinical Research Fellowship). GMM is supported by the National Health and Medical Research Council, the Cancer Institute NSW, the Children's Cancer Institute Australia for Medical Research and the Cancer Council NSW. We thank Dr Patricia Dahia for the gift of PTEN cDNA and Dr Kristen Neville (supported by a grant from the Sydney Children's Hospital Foundation) for the provision of serum from age-matched normal children for the measurement of IGFBP-2.

Author information

Authors and Affiliations

  1. DJ Marsh is a Cancer Institute NSW Fellow and Principal Research Fellow, JL Martin is a Cancer Institute NSW Fellow and Senior Research Fellow, WY Chee is a postgraduate student, and RC Baxter is Director, all at the Kolling Institute of Medical Research, University of Sydney and Royal North Shore Hospital, Sydney, NSW, Australia.,

    Deborah J Marsh, Janet L Martin, Wey Yeeng Chee & Robert C Baxter

  2. J Walker is a Pediatric Endocrinologist at the Department of Pediatric Endocrinology, EP Kirk is a Clinical Geneticist in the Department of Medical Genetics, TN Trahair is a Staff Specialist at the Centre for Children's Cancer and Blood Disorders, and GM Marshall is a Pediatric Hematologist and Oncologist and Director of the Centre for Children's Cancer and Blood Disorders, all at Sydney Children's Hospital, and the School of Women's and Children's Health, University of New South Wales, Sydney.,

    Toby N Trahair, Jan Walker, Edwin P Kirk & Glenn M Marshall

  3. GM Marshall is also Head of the Molecular Carcinogenesis Program, and TN Trahair is also Clinical Research Fellow, at the Children's Cancer Institute Australia, Sydney.,

    Glenn M Marshall

Authors
  1. Deborah J Marsh
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  2. Toby N Trahair
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  3. Janet L Martin
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  4. Wey Yeeng Chee
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  7. Robert C Baxter
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Corresponding author

Correspondence to Glenn M Marshall.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Figure 1

Effects of PTEN expression on phosphorylated S6 kinase. (PPT 81 kb)

Supplementary Figure 2

Effects of PTEN expression and rapamycin treatment on phosphorylated S6 kinase. (PPT 204 kb)

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Marsh, D., Trahair, T., Martin, J. et al. Rapamycin treatment for a child with germline PTEN mutation. Nat Rev Clin Oncol 5, 357–361 (2008). https://doi.org/10.1038/ncponc1112

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