Somatic genomic alterations in retinoblastoma beyond RB1 are rare and limited to copy number changes
| Autor: | Gertjan J.L. Kaspers, Charlotte J. Dommering, Annette C. Moll, Annemarie H. van der Hout, Najim Ameziane, Saskia E. van Mil, Josephine C. Dorsman, Yne de Vries, Jacqueline Cloos, Hanne Meijers-Heijboer, Hein te Riele, Maarten P.G. Massink, Berber M. Mol, Irsan E. Kooi |
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| Přispěvatelé: | Human genetics, CCA - Cancer biology, Pediatric surgery, Ophthalmology, EMGO - Quality of care, ICaR - Circulation and metabolism, Hematology laboratory |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
SEQUENCING DATA Ubiquitin-Protein Ligases Gene Dosage PROGRESSION Biology Gene mutation CHROMOSOMAL INSTABILITY medicine.disease_cause Gene dosage Article 03 medical and health sciences 0302 clinical medicine Chromosome instability medicine Humans GENE-PRODUCT Exome sequencing Genetics Retinoblastoma Binding Proteins Mutation Multidisciplinary CHILDHOOD-CANCER Retinoblastoma RUBINSTEIN-TAYBI SYNDROME MUTATIONS Sequence Analysis DNA medicine.disease TUMORS eye diseases 030104 developmental biology 030220 oncology & carcinogenesis INACTIVATION Carcinogenesis HYBRIDIZATION |
| Zdroj: | Scientific Reports Kooi, I E, Mol, B M, Massink, M P G, Ameziane, N, Meijers-Heijboer, H, Dommering, C J, van Mil, S E, de Vries, Y, van der Hout, A H, Kaspers, G J L, Moll, A C, te Riele, H, Cloos, J & Dorsman, J C 2016, ' Somatic genomic alterations in retinoblastoma beyond RB1 are rare and limited to copy number changes ', Scientific Reports, vol. 6 . https://doi.org/10.1038/srep25264 Scientific Reports, 6:25264. Nature Publishing Group Scientific Reports, 6. Nature Publishing Group |
| ISSN: | 2045-2322 |
| Popis: | Retinoblastoma is a rare childhood cancer initiated by RB1 mutation or MYCN amplification, while additional alterations may be required for tumor development. However, the view on single nucleotide variants is very limited. To better understand oncogenesis, we determined the genomic landscape of retinoblastoma. We performed exome sequencing of 71 retinoblastomas and matched blood DNA. Next, we determined the presence of single nucleotide variants, copy number alterations and viruses. Aside from RB1, recurrent gene mutations were very rare. Only a limited fraction of tumors showed BCOR (7/71, 10%) or CREBBP alterations (3/71, 4%). No evidence was found for the presence of viruses. Instead, specific somatic copy number alterations were more common, particularly in patients diagnosed at later age. Recurrent alterations of chromosomal arms often involved less than one copy, also in highly pure tumor samples, suggesting within-tumor heterogeneity. Our results show that retinoblastoma is among the least mutated cancers and signify the extreme sensitivity of the childhood retina for RB1 loss. We hypothesize that retinoblastomas arising later in retinal development benefit more from subclonal secondary alterations and therefore, these alterations are more selected for in these tumors. Targeted therapy based on these subclonal events might be insufficient for complete tumor control. |
| Databáze: | OpenAIRE |
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