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 simi

SUBMITTER: Imbert-Bouteille M 

PROVIDER: S-EPMC6900371 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature