Novel RB1 and MET Gene Mutations in a Case with Bilateral Retinoblastoma Followed by Multiple Metastatic Osteosarcoma.

Autor: Mokánszki A; Department of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary., Chang Chien YC; Department of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary., Mótyán JA; Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary., Juhász P; Department of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary., Bádon ES; Department of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary., Madar L; Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, H-4032 Debrecen, Hungary.; Division of Clinical Genetics, Department of Laboratory Medicine, Faculty of Medicine University of Debrecen, H-4032 Debrecen, Hungary., Szegedi I; Department of Pediatrics, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary., Kiss C; Department of Pediatrics, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary., Méhes G; Department of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.
Jazyk: angličtina
Zdroj: Diagnostics (Basel, Switzerland) [Diagnostics (Basel)] 2020 Dec 25; Vol. 11 (1). Date of Electronic Publication: 2020 Dec 25.
DOI: 10.3390/diagnostics11010028
Abstrakt: Retinoblastoma (Rb) is a malignant tumor of the developing retina that affects children before the age of five years in association with inherited or early germline mutations of the RB1 gene. The genetic predisposition is also a driver for other primary malignancies, which have become the leading cause of death in retinoblastoma survivors. Other malignancies can occur as a consequence of radiotherapy. We describe a patient with retinoblastoma in which we detected a novel RB1 c.2548C > T, p.(Gln850Ter) and a synchronous MET c.3029C > T, p.(Thr1010Ile) mutation as well. After presenting with bilateral retinoblastoma, the patient developed at least four different manifestations of two independent osteosarcomas. Our goal was to identify all germline and somatic genetic alterations in available tissue samples from different time periods and to reconstruct their clonal relations using next generation sequencing (NGS). We also used structural and functional prediction of the mutant RB and MET proteins to find interactions between the defected proteins with potential causative role in the development of this unique form of retinoblastoma. Both histopathology and NGS findings supported the independent nature of a chondroblastic osteosarcoma of the irradiated facial bone followed by an osteoblastic sarcoma of the leg (tibia).
Databáze: MEDLINE
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