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

Yoshiko Nakano; Meryl Acker; Harriet Druker; Kalene van Engelen; M Stephen Meyn; Jonathan D Wasserman; Rosemarie E Venier; Catherine Goudie; Ana Stosic; Annie Huang; Mary-Louise C Greer; David Malkin; Anita Villani; Bailey Gallinger

doi:10.1038/s41431-024-01674-z

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

Eur J Hum Genet. 2024 Aug 8. doi: 10.1038/s41431-024-01674-z. Online ahead of print.

Authors

Yoshiko Nakano^#^{1

2}, Meryl Acker^#³, Harriet Druker⁴, Kalene van Engelen⁵, M Stephen Meyn⁶, Jonathan D Wasserman^{2

7}, Rosemarie E Venier^{3

8}, Catherine Goudie⁹, Ana Stosic³, Annie Huang^{1

2}, Mary-Louise C Greer¹⁰, David Malkin^{1

2

3}, Anita Villani^{11

12}, Bailey Gallinger^{3

4

8}

Affiliations

¹ Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada.
² Department of Pediatrics, University of Toronto, Toronto, ON, Canada.
³ Genetics and Genome Biology Program, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
⁴ Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
⁵ Medical Genetics Program of Southwestern Ontario, London Health Sciences Centre, London, ON, Canada.
⁶ Center for Human Genomics and Precision Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
⁷ Division of Endocrinology, The Hospital for Sick Children, Toronto, ON, Canada.
⁸ Department of Genetic Counselling, University of Toronto, Toronto, ON, Canada.
⁹ Department of Pediatrics, McGill University Health Centre, Montreal, QC, Canada.
¹⁰ Department of Diagnostic and Interventional Radiology, The Hospital for Sick Children, Department of Medical Imaging, University of Toronto, Toronto, ON, Canada.
¹¹ Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada. anita.villani@sickkids.ca.
¹² Department of Pediatrics, University of Toronto, Toronto, ON, Canada. anita.villani@sickkids.ca.

^# Contributed equally.

PMID: 39117932
DOI: 10.1038/s41431-024-01674-z

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.