Embryonal rhabdomyosarcoma in a patient with a germline CBL pathogenic variant

Jianling Ji; Fariba Navid; Mathew C Hiemenz; Maki Kaneko; Shengmei Zhou; Sulagna C Saitta; Jaclyn A Biegel

doi:10.1016/j.cancergen.2018.12.006

Embryonal rhabdomyosarcoma in a patient with a germline CBL pathogenic variant

Cancer Genet. 2019 Feb:231-232:62-66. doi: 10.1016/j.cancergen.2018.12.006. Epub 2018 Dec 30.

Authors

Jianling Ji¹, Fariba Navid², Mathew C Hiemenz³, Maki Kaneko⁴, Shengmei Zhou³, Sulagna C Saitta³, Jaclyn A Biegel³

Affiliations

¹ Department of Pathology & Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA; Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: jji@chla.usc.edu.
² Hematology, Oncology and Blood and Marrow Transplantation, Children's Hospital Los Angeles, Los Angeles, CA, USA; Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
³ Department of Pathology & Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA; Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁴ Department of Pathology & Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA.

Abstract

Germline pathogenic variants in CBL are associated with an autosomal dominant RASopathy and an increased risk for malignancies, particularly juvenile myelomonocytic leukemia. Herein, we describe a patient with clinical features of a Noonan-spectrum disorder who developed embryonal rhabdomyosarcoma of the bladder at age two years. Tumor analysis using the OncoKids^® cancer panel revealed a CBL pathogenic variant: NM_005188.3:c.1100A>C (p.Gln367Pro). Sanger sequencing of peripheral blood DNA confirmed a de novo heterozygous germline variant. This is the first report of embryonal rhabdomyosarcoma in association with a germline CBL pathogenic variant, further broadening the CBL cancer predisposition spectrum.

Keywords: CBL; Cancer predisposition; Embryonal rhabdomyosarcoma; RASopathy.

Published by Elsevier Inc.

Publication types

Case Reports

MeSH terms

Child, Preschool
Germ-Line Mutation / genetics*
Humans
Male
Proto-Oncogene Proteins c-cbl / genetics*
Rhabdomyosarcoma, Embryonal / genetics*
Rhabdomyosarcoma, Embryonal / pathology

Substances

Proto-Oncogene Proteins c-cbl
CBL protein, human

Grants and funding

P30 CA014089/CA/NCI NIH HHS/United States