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 maligna...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-12-01
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| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.913 |
| _version_ | 1797847632953999360 |
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| author | Marion Imbert‐Bouteille Marion Gauthier‐Villars Dominique Leroux Isabelle Meunier Isabelle Aerts Livia Lumbroso‐Le Rouic Sophie Lejeune Capucine Delnatte Caroline Abadie Pascal Pujol Claude Houdayer Carole Corsini |
| author_facet | Marion Imbert‐Bouteille Marion Gauthier‐Villars Dominique Leroux Isabelle Meunier Isabelle Aerts Livia Lumbroso‐Le Rouic Sophie Lejeune Capucine Delnatte Caroline Abadie Pascal Pujol Claude Houdayer Carole Corsini |
| author_sort | Marion Imbert‐Bouteille |
| collection | DOAJ |
| description | 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 In eight additional similar cases from published and unpublished reports of families, first primary osteosarcomas and sarcomas mostly developed in RB1 low‐penetrance mutation carriers without prior Rb.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. |
| first_indexed | 2024-04-09T18:14:35Z |
| format | Article |
| id | doaj.art-6ef236193ee4411a8cecb491cfe6ec97 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-04-09T18:14:35Z |
| publishDate | 2019-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-6ef236193ee4411a8cecb491cfe6ec972023-04-13T05:27:13ZengWileyMolecular Genetics & Genomic Medicine2324-92692019-12-01712n/an/a10.1002/mgg3.913Osteosarcoma without prior retinoblastoma related to RB1 low‐penetrance germline pathogenic variants: A novel type of RB1‐related hereditary predisposition syndrome?Marion Imbert‐Bouteille0Marion Gauthier‐Villars1Dominique Leroux2Isabelle Meunier3Isabelle Aerts4Livia Lumbroso‐Le Rouic5Sophie Lejeune6Capucine Delnatte7Caroline Abadie8Pascal Pujol9Claude Houdayer10Carole Corsini11Medical Genetics Department CHU Montpellier, Univ Montpellier Montpellier FranceDepartment of Tumour Biology Institut Curie, University Paris Descartes Paris FranceMedical Genetics Department CHU Grenoble Grenoble FranceNational Centre for Rare Diseases, Hereditary Retinal and Optic Nerve Disorders CHU Montpellier, Univ Montpellier Montpellier FranceDepartment of Pediatric Oncology Institut Curie, University Paris Descartes Paris FranceDepartment of Ocular Oncology Institut Curie Paris FranceMedical Genetics Department CHRU Lille Lille FranceOncogenetics Institut de Cancérologie de l'Ouest site René Gauducheau Saint Herblain FranceOncogenetics Institut de Cancérologie de l'Ouest site René Gauducheau Saint Herblain FranceMedical Genetics Department CHU Montpellier, Univ Montpellier Montpellier FranceDepartment of Tumour Biology Institut Curie, University Paris Descartes Paris FranceMedical Genetics Department CHU Montpellier, Univ Montpellier Montpellier FranceAbstract 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://doi.org/10.1002/mgg3.913cancer screeninglow penetranceOsteosarcomaRB1Sarcomawhole‐body MRI |
| spellingShingle | Marion Imbert‐Bouteille Marion Gauthier‐Villars Dominique Leroux Isabelle Meunier Isabelle Aerts Livia Lumbroso‐Le Rouic Sophie Lejeune Capucine Delnatte Caroline Abadie Pascal Pujol Claude Houdayer Carole Corsini 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 cancer screening low penetrance Osteosarcoma RB1 Sarcoma whole‐body MRI |
| title | Osteosarcoma without prior retinoblastoma related to RB1 low‐penetrance germline pathogenic variants: A novel type of RB1‐related hereditary predisposition syndrome? |
| title_full | Osteosarcoma without prior retinoblastoma related to RB1 low‐penetrance germline pathogenic variants: A novel type of RB1‐related hereditary predisposition syndrome? |
| title_fullStr | Osteosarcoma without prior retinoblastoma related to RB1 low‐penetrance germline pathogenic variants: A novel type of RB1‐related hereditary predisposition syndrome? |
| title_full_unstemmed | Osteosarcoma without prior retinoblastoma related to RB1 low‐penetrance germline pathogenic variants: A novel type of RB1‐related hereditary predisposition syndrome? |
| title_short | Osteosarcoma without prior retinoblastoma related to RB1 low‐penetrance germline pathogenic variants: A novel type of RB1‐related hereditary predisposition syndrome? |
| title_sort | osteosarcoma without prior retinoblastoma related to rb1 low penetrance germline pathogenic variants a novel type of rb1 related hereditary predisposition syndrome |
| topic | cancer screening low penetrance Osteosarcoma RB1 Sarcoma whole‐body MRI |
| url | https://doi.org/10.1002/mgg3.913 |
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