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Whole exome sequencing on primary retinoblastoma tissues and matching lymphocyte DNA.

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.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001001909 Illumina HiSeq 2500 143
Publications Citations
Somatic genomic alterations in retinoblastoma beyond RB1 are rare and limited to copy number changes.
Sci Rep 6: 2016 25264
RB1 loss triggers dependence on ESRRG in retinoblastoma.
Sci Adv 8: 2022 eabm8466
High-Level <i>MYCN-</i>Amplified <i>RB1-</i>Proficient Retinoblastoma Tumors Retain Distinct Molecular Signatures.
Ophthalmol Sci 2: 2022 100188