Skip to Main content Skip to Navigation
Journal articles

Osteosarcoma without prior retinoblastoma related to RB1 low‐penetrance germline pathogenic variants: A novel type of RB1 ‐related hereditary predisposition syndrome?

Abstract : Background: Retinoblastoma (Rb) is a rare intraocular malignant tumor in children with high overall survival. Predisposition to Rb is linked to RB1 germline mutations with high penetrance, but rare RB1 low‐penetrance variants are also known. Rb survivors are at risk of second primary malignancies (SPMs), mostly osteosarcoma and soft‐tissue sarcoma. Nevertheless, the risk of primary osteosarcoma developing without prior Rb has not been reported in RB1 germline mutation carriers. Methods: We report a patient in whom osteosarcoma developed at age 17 as a first primary malignancy within a family context of sarcoma. Results: Unexpectedly, genetic testing identified a low‐penetrance germline mutation in RB1 [NM_000321.2: c.45_76dup; p.(Pro26Leufs*50)]. In eight additional similar cases from published and unpublished reports of families, first primary osteosarcomas and sarcomas mostly developed in RB1 low‐penetrance mutation carriers without prior Rb. Conclusion: We propose that first primary sarcoma and osteosarcoma could be a novel clinical presentation of a RB1‐related hereditary predisposition syndrome linked to RB1 low‐penetrance germline mutations. In these families, careful screening of primary non‐Rb cancer and SPMs is required by maintaining enhanced clinical vigilance. Implementing lifelong periodic whole‐body MRI screening might be a complementary strategy for unaffected carrier relatives in these families.
Document type :
Journal articles
Complete list of metadatas

https://hal-normandie-univ.archives-ouvertes.fr/hal-02376947
Contributor : Claude Houdayer <>
Submitted on : Friday, November 22, 2019 - 7:02:14 PM
Last modification on : Tuesday, September 22, 2020 - 3:55:42 AM

Links full text

Identifiers

Citation

Marion Imbert‐bouteille, Marion Gauthier‐villars, Dominique Leroux, Isabelle Meunier, Isabelle Aerts, et al.. Osteosarcoma without prior retinoblastoma related to RB1 low‐penetrance germline pathogenic variants: A novel type of RB1 ‐related hereditary predisposition syndrome?. Molecular Genetics & Genomic Medicine, Wiley Periodicals, Inc. 2019, 7, pp.e913. ⟨10.1002/mgg3.913⟩. ⟨hal-02376947⟩

Share

Metrics

Record views

134