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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similar cases from published and unpublished reports of families, first primary osteosarcomas and sarcomas mostly developed in RB1 low‐penetrance mutation carriers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.
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
Contributor : Claude Houdayer <>
Submitted on : Friday, November 22, 2019 - 7:02:14 PM
Last modification on : Tuesday, September 22, 2020 - 3:55:42 AM
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