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Novel germline RB1 and MET gene mutations in a case with bilateral retinoblastoma followed by multiple metastatic osteosarcoma
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  • Attila Mokánszki,
  • Chang Yi-Che,
  • János Mótyán,
  • Péter Juhász,
  • Emese Bádon,
  • László Madar,
  • István Szegedi,
  • Csongor Kiss,
  • Gábor Méhes
Attila Mokánszki
University of Debrecen Faculty of Medicine
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Chang Yi-Che
University of Debrecen Faculty of Medicine
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János Mótyán
University of Debrecen Faculty of Medicine
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Péter Juhász
University of Debrecen Faculty of Medicine
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Emese Bádon
University of Debrecen Faculty of Medicine
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László Madar
University of Debrecen Faculty of Medicine
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István Szegedi
University of Debrecen Faculty of Medicine
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Csongor Kiss
University of Debrecen
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Gábor Méhes
University of Debrecen Faculty of Medicine
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Abstract

Background 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 related with second primary malignancies arising de novo, or following radiotherapy which have become the leading cause of death in retinoblastoma survivors. Procedure We describe a retinoblastoma case with a novel RB1 and a synchronous MET aberration. 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 uniqe form of retinoblastoma. Results In this study we detected a retinoblastoma case of non-parental origin with a novel RB1 c.2548C>T;p.(Gln850Ter) and a synchronous MET c.3029C>T;p.(Thr1010Ile) germline mutations. Following bilateral retinoblastoma the boy further developed at least four different manifestations of two independent osteosarcomas. 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). Conclusions Because of the expanding number of registered Rb cases, the novel rare cases publication is very important to understand the molecular mechanism of this malignancy. We reported a novel form of Rb and consequential chondroblastic and osteoblastic osteosarcoma, the latter one developing pulmonary metastatses.

Peer review status:Published

25 Dec 2020Published in Diagnostics volume 11 issue 1 on pages 28. 10.3390/diagnostics11010028