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Late-onset tumors in rhabdoid tumor predisposition syndrome type-1 (RTPS1) and implications for surveillance

European Journal of Human Genetics (2024)Cite this article

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Abstract

Rhabdoid tumor predisposition syndrome type-1 (RTPS1) is characterized by germline pathogenic variants in SMARCB1 and development of INI1-deficient rhabdoid tumors in early childhood. Due to its poor prognosis, the risk of subsequent tumor development and the impact of surveillance at later ages are poorly understood. We retrospectively reviewed individuals referred to the Cancer Genetics Program at The Hospital for Sick Children for SMARCB1 genetic testing and/or surveillance for RTPS1. In addition, to explore characteristics of late-onset tumors in RTPS1, a literature review was conducted. Of eighty-three individuals (55 probands and 28 family members), 12 probands and 4 family members were genetically confirmed with RTPS1. Four pediatric probands with RTPS1 underwent surveillance. An additional three individuals, including one patient with 22q11.2 distal deletion without history of tumor, one patient with negative genetic testing results but clinically diagnosed with RTPS1, and one sibling identified through cascade testing, underwent surveillance. Three patients with RTPS1 developed tumors between the ages of 9 and 17, including malignant rhabdoid tumors (N = 3), schwannomas (N = 4), and epithelioid malignant peripheral nerve sheath tumor (N = 1). Three of these lesions were asymptomatically detected by surveillance. A literature review revealed 17 individuals with RTPS1 who developed INI1-deficient tumors after age five. Individuals with RTPS1 remain at elevated risk for developing INI1-deficient tumors after the peak age of rhabdoid tumor in early childhood. Extension of surveillance beyond 5 years of age could lead to improved survival and reduced morbidity for these patients, and prospective evaluation of revised approaches will be important.

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Acknowledgements

YN is supported in part with funds from Jeffrey Brock Cancer Genetics Research Fellowship, Garron Family Cancer Center Research Fellowship/Scotiabank Clinician Scientist Fellowship, Hold’em for Life Oncology Fellowship, and Tokyo Children’s Cancer Study Group scholarship of the Gold Ribbon Network. DM hold the CIBC Children’s Foundation Chair in Child Health Research.

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Author notes

  1. These authors contributed equally: Yoshiko Nakano, Meryl Acker.

  2. These authors jointly supervised this work: Anita Villani, Bailey Gallinger.

Authors and Affiliations

  1. Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada

    Yoshiko Nakano, Annie Huang, David Malkin & Anita Villani

  2. Department of Pediatrics, University of Toronto, Toronto, ON, Canada

    Yoshiko Nakano, Jonathan D. Wasserman, Annie Huang, David Malkin & Anita Villani

  3. Genetics and Genome Biology Program, The Hospital for Sick Children Research Institute, Toronto, ON, Canada

    Meryl Acker, Rosemarie E. Venier, Ana Stosic, David Malkin & Bailey Gallinger

  4. Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada

    Harriet Druker & Bailey Gallinger

  5. Medical Genetics Program of Southwestern Ontario, London Health Sciences Centre, London, ON, Canada

    Kalene van Engelen

  6. Center for Human Genomics and Precision Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    M. Stephen Meyn

  7. Division of Endocrinology, The Hospital for Sick Children, Toronto, ON, Canada

    Jonathan D. Wasserman

  8. Department of Genetic Counselling, University of Toronto, Toronto, ON, Canada

    Rosemarie E. Venier & Bailey Gallinger

  9. Department of Pediatrics, McGill University Health Centre, Montreal, QC, Canada

    Catherine Goudie

  10. Department of Diagnostic and Interventional Radiology, The Hospital for Sick Children, Department of Medical Imaging, University of Toronto, Toronto, ON, Canada

    Mary-Louise C. Greer

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  1. Yoshiko Nakano
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Contributions

YN, and MA, AV, and BG, led the study and wrote the manuscript. DM, AV, AV, and BG, supervised the study. HD, KE, MSM, JDW, REV, CG, AS, AH, and MLG provided valuable input regarding study design, data analysis, interpretation of results, and writing the manuscript.

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Correspondence to Anita Villani.

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This study was approved by the Research Ethics Board (REB#1000053261) at the Hospital for Sick Children (SickKids; Toronto, Canada).

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Nakano, Y., Acker, M., Druker, H. et al. Late-onset tumors in rhabdoid tumor predisposition syndrome type-1 (RTPS1) and implications for surveillance. Eur J Hum Genet (2024). https://doi.org/10.1038/s41431-024-01674-z

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  • DOI: https://doi.org/10.1038/s41431-024-01674-z

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